cas 36640-40-1, 3-(4-FLUORO-PHENYL)-1-PHENYL-1H-PYRAZOLE-4-CARBALDEHYDE

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Design, synthesis, biological evaluation, and molecular docking studies of some novel N,N-dimethylaminopropoxy-substituted aurones
In continuation of our ongoing research on the discovery of novel and potentially bioactive aurones, we have designed and synthesized some novel N,N-dimethylaminopropoxy-substituted pyrazole-based aurones 10(a-l). These pyrazole-benzofuranone hybrid compounds were characterized by using their IR, 1H-NMR, 13C-NMR, and mass spectrometry data. Compound 10c was used as a model to further explicate the structure of tilted compounds by means of 1H-1H COSY, 1H-13C HMQC, 1H-13C HMBC, 1H-1H TOCSY, 1H-1H NOSEY, DEPT-45°, DEPT-90°, and DEPT-135° NMR spectra. The comparative molecular docking study of N,N-dimethylaminopropoxy-substituted pyrazole-based aurones and standard drugs (Ampicillin and Chloramphenicol) against Bacillus subtilis (PDB: 6tzp) active site was performed to determine the binding interactions, binding energy, and orientation of the molecules at the active site of the target protein. Out of these synthesized compounds, five best analogs (10b, 10f, 10h, 10k, and 10l) of docking results were also evaluated for their in vitro antibacterial potential against Bacillus subtilis to validate the docking results.
Kumar, Gourav,Saroha, Bhavna,Kumar, Ramesh,Kumari, Meena,Dalal, Sunita,Kumar, Suresh
p. 297 - 308
(2021/10/25)

Synthesis of lathyrane diterpenoid nitrogen-containing heterocyclic derivatives and evaluation of their anti-inflammatory activities
As our ongoing work on lathyrane diterpenoid derivatization, three series of lathyrane diterpenoid derivatives were designed and synthesized based combination principles, including pyrazole, thiazole and furoxan moieties. Biological evaluation indicated t
Wang, Wang,Xiong, Liangliang,Li, Yutong,Song, Zhuorui,Sun, Dejuan,Li, Hua,Chen, Lixia
(2022/01/24)

Design and synthesis of novel quinazolinone-pyrazole derivatives as potential α-glucosidase inhibitors: Structure-activity relationship, molecular modeling and kinetic study
In this study, a new series of quinazolinone-pyrazole hybrids were designed, synthesized and screened for their α-glucosidase inhibitory activity. The results of the in vitro screening indicated that all the molecular hybrids exhibited more inhibitory activity (IC50 values ranging from 60.5 ± 0.3 μM-186.6 ± 20 μM) in comparison to standard acarbose (IC50 = 750.0 ± 10.0 μM). Limited structure–activity relationship suggested that the variation in the inhibitory activities of the compounds affected by different substitutions on phenyl rings of diphenyl pyrazole moiety. The enzyme kinetic studies of the most potent compound 9i revealed that it inhibited α-glucosidase in a competitive mode with a Ki of 56 μM. Molecular docking study was performed to predict the putative binding interaction. As expected, all pharmacophoric moieties used in the initial structure design playing a pivotal role in the interaction with the binding site of the enzyme. In addition, by performing molecular dynamic investigation and MM-GBSA calculation, we investigated the difference in structural perturbation and dynamic behavior that is observed over α-glycosidase in complex with the most active compound and acarbose relative to unbound α-glycosidase enzyme.
Azimi, Fateme,Azizian, Homa,Najafi, Mohammad,Hassanzadeh, Farshid,Sadeghi-aliabadi, Hojjat,Ghasemi, Jahan B.,Ali Faramarzi, Mohammad,Mojtabavi, Somayeh,Larijani, Bagher,Saghaei, Lotfollah,Mahdavi, Mohammad
(2021/07/13)

H3PO4 catalyzed one-pot synthesis of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde to novel 1,3-diphenyl-1H-pyrazole-4-carbonitrile
Abstract: One-pot condensation of pyrazole-4-aldehydes and hydroxylamine hydrochloride to form the corresponding oxime using formic acid as a medium and further dehydration of oxime using a catalytic amount of orthophosphoric acid to afford novel pyrazole-4-carbonitrile. This protocol serves as an ortho-phosphoric acid-catalyzed one-pot conversion of aldehyde to nitrile. Most remarkable features of this method are metal-free, cost-effective, atom efficiency with excellent yield (98–99%). This process will serve as a robust and scalable tool for the synthesis of valuable and versatile precursor (nitriles). This precursor will pave the way for the synthesis of various medicinally important valuable compounds. Graphic abstract: [Figure not available: see fulltext.].
Choudhare, Tukaram S,Netankar, Prashant D,Shirsath, Sagar E,Wagare, Devendra S
(2021/07/10)

Design and synthesis of pyrazole–pyrazoline hybrids as cancer-associated selective COX-2 inhibitors
In continuation of our previous work on cancer and inflammation, 15 novel pyrazole–pyrazoline hybrids (WSPP1–15) were synthesized and fully characterized. The formation of the pyrazoline ring was confirmed by the appearance of three doublets of doublets in 1H nuclear magnetic resonance spectra exhibiting an AMX pattern for three protons (HA, HM, and HX) of the pyrazoline ring. All the synthesized compounds were screened for their in vitro anticancer activity against five cell lines, that is, MCF-7, A549, SiHa, COLO205, and HepG2 cells, using the MTT growth inhibition assay. 5-Fluorouracil was taken as the positive control in the study. It was observed that, among them, WSPP11 was found to be active against A549, SiHa, COLO205, and HepG2 cells, with IC50 values of 4.94, 4.54, 4.86, and 2.09 μM. All the derivatives were also evaluated for their cytotoxicity against HaCaT cells. WSPP11 was also found to be nontoxic against normal cells (cell line HaCaT), with an IC50 value of more than 50 μM. The derivatives were also evaluated for their in vitro anti-inflammatory activity by the protein (egg albumin) denaturation assay and the red blood cell membrane stabilizing assay, using diclofenac sodium and celecoxib as standard. Compounds that showed significant anticancer and anti-inflammatory activities were further studied for COX-2 inhibition. The manifestation of a higher COX-2 selectivity index of WSPP11 as compared with other derivatives and an in vitro anticancer activity against four cell lines further established that compounds that were more selective toward COX-2 also exhibited a better spectrum of activity against various cancer cell lines.
Akhtar, Wasim,Marella, Akranth,Alam, Mohammad Mumtaz,Khan, Mohemmed F.,Akhtar, Mymoona,Anwer, Tariq,Khan, Farah,Naematullah, Md.,Azam, Faizul,Rizvi, Moshahid A.,Shaquiquzzaman, Mohammad
(2020/10/09)

Design and synthesis of novel pyrazole-phenyl semicarbazone derivatives as potential α-glucosidase inhibitor: Kinetics and molecular dynamics simulation study
A series of novel pyrazole-phenyl semicarbazone derivatives were designed, synthesized, and screened for in vitro α-glucosidase inhibitory activity. Given the importance of hydrogen bonding in promoting the α-glucosidase inhibitory activity, pharmacophore modification was established. The docking results rationalized the idea of the design. All newly synthesized compounds exhibited excellent in vitro yeast α-glucosidase inhibition (IC50 values in the range of 65.1–695.0 μM) even much more potent than standard drug acarbose (IC50 = 750.0 μM). Among them, compounds 8o displayed the most potent α-glucosidase inhibitory activity (IC50 = 65.1 ± 0.3 μM). Kinetic study of compound 8o revealed that it inhibited α-glucosidase in a competitive mode (Ki = 87.0 μM). Limited SAR suggested that electronic properties of substitutions have little effect on inhibitory potential of compounds. Cytotoxic studies demonstrated that the active compounds (8o, 8k, 8p, 8l, 8i, and 8a) compounds are also non-cytotoxic. The binding modes of the most potent compounds 8o, 8k, 8p, 8l and 8i was studied through in silico docking studies. Molecular dynamic simulations have been performed in order to explain the dynamic behavior and structural changes of the systems by the calculation of the root mean square deviation (RMSD) and root mean square fluctuation (RMSF).
Azimi, Fateme,Ghasemi, Jahan B.,Azizian, Homa,Najafi, Mohammad,Faramarzi, Mohammad Ali,Saghaei, Lotfollah,Sadeghi-aliabadi, Hojjat,Larijani, Bagher,Hassanzadeh, Farshid,Mahdavi, Mohammad
p. 1082 - 1095
(2020/11/20)

In vitro studies of potent aldose reductase inhibitors: Synthesis, characterization, biological evaluation and docking analysis of rhodanine-3-hippuric acid derivatives
Inhibitors of aldose reductase are rate-limiting enzymes and could play a key role to prevent the complications of diabetes. In our attempt to develop novel inhibitors of aldose reductase, the derivatives of rhodanine-3-hippuric acid-pyrazole hybrid were synthesized and characterised by spectral data. The biological studies reveal that all the compounds show an excellent activity against ALR2 with IC50 values ranging from 0.04 to 1.36 μM. Among these the synthesised compounds 6a-m, 6g and 6e showed specific inhibitory activity with IC50 values of 0.04 and 0.06 μM respectively against ALR2 and found to be more potent than epalrestat (IC50 = 0.87 μM), the only aldose reductase inhibitor currently used in the therapy. Molecular docking analysis using the AR-NADP+ complex as a receptor was performed with all the synthesized compounds. All the compounds exhibit a well-defined binding mode within the AR active site, similarly to previous described AR inhibitors, with the anion head group bound to the catalytic center, blocking thus its activity. By forming hydrogen bonds with Tyr48 and His110 of the protein from ALR2 (PDB ID: 2FZD), the compounds 6g and 6e interrupt the proton donation mechanism, which is necessary for the catalytic activity of ALR2.
Celestina, Stephen Kumar,Ravi, Subban,Sundaram, Kaveri
(2020/02/22)

New library of pyrazole–imidazo[1,2-α]pyridine molecular conjugates: Synthesis, antibacterial activity and molecular docking studies
A library of novel pyrazole–imidazo[1,2-α]pyridine scaffolds was designed and synthesized through a one-pot three-component tandem reaction. The structures of synthesized conjugates were confirmed by spectroscopic techniques (NMR, IR and HRMS). In vitro antibacterial evaluation of the twelve synthesized molecules (7a, 8a–k) against methicillin-resistant Staphylococcus aureus and normal strains of Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia and Pseudomonas aeruginosa established 8b, 8d, 8e, 8h and 8i as potent antibacterial agents with superior minimum bactericidal concentration, compared with standard drug ciprofloxacin. Molecular docking studies of all active compounds into the binding site of glucosamine-6-phosphate synthase were further performed in order to have a comprehensive understanding of putative binding modes within the active sites of the receptor.
Ebenezer, Oluwakemi,Awolade, Paul,Koorbanally, Neil,Singh, Parvesh
p. 162 - 173
(2019/11/03)

Novel pyrazole-clubbed thiophene derivatives via Gewald synthesis as antibacterial and anti-inflammatory agents
The aim of this study was to synthesize newer potent Schiff bases by condensing 2-amino-5-(2,4-dichlorophenyl)thiophene-3-carbonitrile and 1,3-disubstituted-1H-pyrazole-4-carbaldehydes, and to investigate their biological activity. The compounds were synthesized via Gewald synthesis and characterized by spectral data and elemental analyses. They were screened for their in vitro antibacterial and anti-inflammatory activities. The synthesized compounds were also evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv using the microplate Alamar Blue assay. Compounds 8b, 8c, 8f, 8g, 8k, 8n, and 8o showed promising antibacterial activity. The interactions between the substituted pyrazoles and bovine protein showed promising anti-inflammatory activity. The experimental results revealed compound 8a as a promising antitubercular agent. Hemolytic assays confirmed that the compounds are nontoxic, with percentage hemolysis ranging from 3.6 to 20.1, at a concentration of 1 mg/ml. The results suggest that the pyrazole ring and the substitution pattern on the heterocyclic moiety have an effect on the bioactivity.
Nayak, Soukhyarani G.,Poojary, Boja,Kamat, Vinuta
(2020/09/09)

Microwave-Assisted Synthesis and Antimicrobial Activity of Novel Pyrazole–Indanone Hybrid Analogs
Abstract: A simple and efficient microwave-assisted protocol has been developed for the synthetic of a series of novel pyrazole–indanone hybrid analogs. The target compounds have been synthesized by the Claisen–Schmidt condensation of different 1,3-diphenyl-1H-pyrazole-4-carbaldehydes with 2,3-dihydro-1H-inden-1-one in the presence of potassium hydroxide. The compounds were characterized by IR, 1H and 13C NMR, and mass spectra and were found to exhibit potent antimicrobial activity in vitro.
Sundergoud, Sh.,Swamy, M. Kumara,Veerasomaiah, P.,Venkatesh, N.
p. 1635 - 1639
(2020/10/22)

Pyrazolylphenanthroimidazole heterocycles: Synthesis, biological and molecular docking studies
The synthesis of a series of novel pyrazolylphenanthroimidazoles 6a-6j has been accomplished utilizing a multi-step synthetic protocol, and characterized through physical and spectral techniques. Among them, the molecules possessing para-bromo (6d), para-methyl (6f) and para-nitro (6j) phenyl substituents on the pyrazole scaffold displayed similar anti-inflammatory activity and the one with no substituents on the aryl unit (6a) exhibited the highest anti-inflammatory profile. While investigating the DPPH radical scavenging activity, the synthesized chemical entity with a para-methoxyphenyl group attached at the pyrazole structural motif (6i) revealed the highest activity when compared to the other synthesized molecules. Furthermore, the evaluation of cytotoxic activity of the synthesized molecule (6a) exerted significant activity against both the pancreatic cell lines such as AsPC1 and SW1990. Besides, while performing the molecular docking studies of 6a with B-cell lymphoma 2, an appreciable binding affinity (-9.04 kcal mol-1) has been observed. The results of the present examination imply that these chemical entities could be used as efficient intermediates for the construction of biopertinent molecules. This journal is
Sivaramakarthikeyan, Ramar,Iniyaval, Shunmugam,Lim, Wei-Meng,Hii, Ling-Wei,Mai, Chun-Wai,Ramalingan, Chennan
p. 19612 - 19622
(2020/12/04)

Synthesis and Pharmacological Screening of Difluorophenyl Pyrazole Chalcone Conjugates as Antifungal, Anti-Inflammatory, and Antioxidant Agents
Abstract: A new series of difluoro phenyl pyrazole chalcone was prepared by utilizing PEG 400 as a catalyst and investigated for their antifungal, anti-inflammatory, and antioxidant activity. The compounds 3-[3-(4-bromo-phenyl)-1-phenyl-1H-pyrazol-4-yl]-1-(2,4-difluloro-phenyl)-propenone (IVc), 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd), 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), and 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg) exhibited promising antifungal activity at MIC of 25 and 50 μg/mL against selected human pathogenic fungi. Synthesized compounds 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd), 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg) and 1-(2,4-difluoro-phenyl)-3-[3-(4-fluoro-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVa) showed good anti-inflammatory activities comparable to the standard drug diclofenac sodium. Compounds 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd) and 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg) showed good hydrogen peroxide scavenging potential as compared to the butylated hydroxyl toluene. The conjugates 1-(2,4-difluoro-phenyl)-3-[3-(4-methoxy-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVe), 1-(2,4-difluoro-phenyl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)-propenone (IVg), and 1-(2,4-difluoro-phenyl)-3-[3-(4-methyl-phenyl)-1-phenyl-1H-pyrazol-4-yl]-propenone (IVd) found more potent than standard ascorbic acid in DPPH radical scavenging assay as well as ferrous reducing power assay. The conjugates showed good interactions with the target protein in docking study.
Bhosale, R. B.,Hublikar, M. G.,Jadhav, S. Y.,Kulkarni, A. A.,Peerzade, N. A.,Varpe, B. D.
p. 1128 - 1135
(2020/12/30)

Targeting malaria and leishmaniasis: Synthesis and pharmacological evaluation of novel pyrazole-1,3,4-oxadiazole hybrids. Part II
In continuance with earlier reported work, an extension has been carried out by the same research group. Mulling over the ongoing condition of resistance to existing antimalarial agents, we had reported synthesis and antimalarial activity of certain pyrazole-1,3,4-oxadiazole hybrid compounds. Bearing previous results in mind, our research group ideated to design and synthesize some more derivatives with varied substitutions of acetophenone and hydrazide. Following this, derivatives 5a–r were synthesized and tested for antimalarial efficacy by schizont maturation inhibition assay. Further, depending on the literature support and results of our previous series, certain potent compounds (5f, 5n and 5r) were subjected to Falcipain-2 inhibitory assay. Results obtained for these particular compounds further strengthened our hypothesis. Here, in this series, compound 5f having unsubstituted acetophenone part and a furan moiety linked to oxadiazole ring emerged as the most potent compound and results were found to be comparable to that of the most potent compound (indole bearing) of previous series. Additionally, depending on the available literature, compounds (5a–r) were tested for their antileishmanial potential. Compounds 5a, 5c and 5r demonstrated dose-dependent killing of the promastigotes. Their IC50 values were found to be 33.3 ± 1.68, 40.1 ± 1.0 and 19.0 ± 1.47 μg/mL respectively. These compounds (5a, 5c and 5r) also had effects on amastigote infectivity with IC50 of 44.2 ± 2.72, 66.8 ± 2.05 and 73.1 ± 1.69 μg/mL respectively. Further target validation was done using molecular docking studies. Acute oral toxicity studies for most active compounds were also performed.
Verma, Garima,Khan, Mohemmed Faraz,Mohan Nainwal, Lalit,Ishaq, Mohd,Akhter, Mymoona,Bakht, Afroz,Anwer, Tariq,Afrin, Farhat,Islamuddin, Mohammad,Husain, Ibraheem,Alam, Mohammad Mumtaz,Shaquiquzzaman, Mohammad
(2019/05/29)

Discovery of 1,3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups as potential PTP1B inhibitors
Two series of 1,3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups were identified as competitive protein tyrosine phosphatase 1B (PTP1B) inhibitors. Among the compounds studied, IIIv was found to have the best in vitro inhibition activity against PTP1B (IC50 = 0.67 ± 0.09 μM) and the best selectivity (9-fold) between PTP1B and T-cell protein tyrosine phosphatase (TCPTP). Molecular docking studies demonstrated that compounds IIIm, IIIv and IVg could occupy simultaneously at both the catalytic site and the adjacent pTyr binding site. These results provide novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.
Sun, Liangpeng,Wang, Peipei,Xu, Lili,Gao, Lixin,Li, Jia,Piao, Huri
p. 1187 - 1193
(2019/03/26)

Synthesis of some hippuric acid substrate linked novel pyrazoles as antimicrobial agents
Escalating resistance of microorganisms to the currently accessible antimicrobial drugs has forced to synthesize some novel biologically active compounds as efficient alternates via economical substrates. Hence, hippuric acid was used as one of the starting materials to synthesize pyrazole derivatives. All the synthesized compounds were characterized by IR, NMR (1H & 13C) and mass spectral data. The antimicrobial potential of synthesized compounds has been explored against four bacterial and two fungal strains. Among the 12 compounds, 3 compounds 8j, 8k and 8l were found to exhibit prominent antimicrobial potential as compared with the standards ciprofloxacin and amphotericin-B.
Verma, Anil,Kumar, Vinod,Khare, Rajshree,Singh, Joginder
p. 522 - 526
(2019/02/06)

Probing the high potency of pyrazolyl pyrimidinetriones and thioxopyrimidinediones as selective and efficient non-nucleotide inhibitors of recombinant human ectonucleotidases
With the aim to discover novel, efficient and selective inhibitors of human alkaline phosphatase and nucleotide pyrophosphatase enzymes, two new series of pyrazolyl pyrimidinetriones (PPTs) (6a–g) and thioxopyrimidinediones (PTPs) (6h–n) were synthesized in good chemical yields using Knoevenagel condensation reaction between pyrazole carbaldehydes (4a–g) and pharmacologically active N-alkylated pyrimidinetrione (5a) and thioxopyrimidinedione (5b). The inhibition potential of the synthesized hybrid compounds was evaluated against human alkaline phosphatase (h-TNAP and h-IAP) and ectonucleotidase (h-NPP1 and h-NPP3) enzymes. Most of the tested analogs were highly potent with a variable degree of inhibition depending on the functionalized hybrid structure. The detailed structure-activity relationship (SAR) of PPT and PTP derivatives suggested that the compound with unsubstituted phenyl ring from PPT series led to selective and potent inhibition (6a; IC50 = 0.33 ± 0.02 μM) of h-TNAP, whereas compound 6c selectively inhibited h-IAP isozyme with IC50 value of 0.86 ± 0.04 μM. Similarly, compounds 6b and 6h were identified as the lead scaffolds against h-NPP1 and h-NPP3, respectively. The probable binding modes for the most potent inhibitors were elucidated through molecular docking analysis. Structure-activity relationships, mechanism of action, cytotoxic effects and druglikeness properties are also discussed.
Andleeb, Hina,Hameed, Shahid,Ejaz, Syeda Abida,Khan, Imtiaz,Zaib, Sumera,Lecka, Joanna,Sévigny, Jean,Iqbal, Jamshed
(2019/04/25)

Unveiling novel diphenyl-1H-pyrazole based acrylates tethered to 1,2,3-triazole as promising apoptosis inducing cytotoxic and anti-inflammatory agents
Meagre and suboptimal therapeutic response along with the side effect profile associated with the existing anticancer therapy have necessitated the development of new therapeutic modalities to curb this disease. Bearing in mind the current scenario, a series of 1,2,3-triazole linked 3-(1,3-diphenyl-1H-pyrazol-4-yl)acrylates was synthesized following a multi-step reaction scheme. Initial screening for anticancer potential was done by in vitro sulforhodamine B assay against four human cancer cell lines- MCF-7 (breast), A549 (Lung) and HCT-116 and HT-29 (Colon). On evaluation, several compounds showed promising growth inhibition against all the cell lines, particularly compounds 6e, 6f and 6n. Among them, compound 6f displayed IC50 values of 1.962, 3.597, 1.764 and 4.496 μM against A549, HCT-116, MCF-7 and HT-29 cell lines respectively. Furthermore, the apoptosis inducing potential of the compounds was determined by Hoechst staining and DNA fragmentation assay. Colony formation inhibition assay was also carried out to determine the long term cytotoxic potential of the molecules. Moreover, compounds 6e, 6f and 6n were also evaluated for anti-inflammatory activity by protein albumin denaturation assay and red blood cell membrane stabilizing assay.
Khan, Mohemmed Faraz,Anwer, Tarique,Bakht, Afroz,Verma, Garima,Akhtar, Wasim,Alam, M. Mumtaz,Rizvi, Moshahid Alam,Akhter, Mymoona,Shaquiquzzaman, Mohammad
p. 667 - 678
(2019/04/05)

Design, synthesis, modeling studies and biological screening of novel pyrazole derivatives as potential analgesic and anti-inflammatory agents
Reported herein are the design, synthesis, and pharmacologic evaluation of novel pyrazole and pyrazoline derivatives. The study presents the effect of lengthening of carbon chain in different pyrazole derivatives bearing various amine moieties. Combinatio
Taher, Azza T.,Mostafa Sarg, Marwa T.,El-Sayed Ali, Nermeen R.,Hilmy Elnagdi, Noha
(2019/06/14)

Pyrazolo-benzothiazole hybrids: Synthesis, anticancer properties and evaluation of antiangiogenic activity using in vitro VEGFR-2 kinase and in vivo transgenic zebrafish model
A series of new pyrazolo-benzothiazole hybrids (7–26) were synthesised and screened for their cytotoxic activity towards several cancer cell lines [colon (HT-29), prostate (PC-3), lung (A549), glioblastoma (U87MG)] and normal human embryonic kidney cell line (Hek-293T). Compounds 8, 9, 13, 14, 18, 19, 23, and 24 displayed significant activity, with compound 14 being particularly potent towards all the tested cancer cell lines with IC50 values in the range 3.17–6.77 μM, even better than reference drug axitinib (4.88–21.7 μM). Compound 14 also showed the strongest growth inhibition in 3D multicellular spheroids of PC-3 and U87MG cells. The mechanism of cellular toxicity in PC-3 cells was found to be cell cycle arrest and apoptosis induction through depolarisation of mitochondrial membrane potential, increased ROS production and subsequent DNA damage. Further, compound 14 displayed significant in vitro (VEGFR-2 inhibition) and in vivo [transgenic zebrafish Tg(flila:EGFP) model] antiangiogenic properties. Overall, these results provide strong evidence that compound 14 could be considered for a lead candidate in anticancer and antiangiogenic drug discovery.
Reddy, Velma Ganga,Reddy, T. Srinivasa,Jadala, Chetna,Reddy, M. Soumya,Sultana, Faria,Akunuri, Ravikumar,Bhargava, Suresh K.,Wlodkowic, Donald,Srihari,Kamal, Ahmed
(2019/08/26)

Synthesis and biological evaluation of thiazolidine-2,4-dione-pyrazole conjugates as antidiabetic, anti-inflammatory and antioxidant agents
A series of fourteen novel thiazolidine-2,4-dione derivatives clubbed with pyrazole moiety were synthesized via four step reaction procedure. Reactions were monitored by thin layer chromatography and were characterized by physicochemical and spectrophotometric (IR, Mass, 1HNMR and 13CNMR) analysis. The spectral data were in good agreement with their structures. The title compounds were docked against peroxisome proliferated activated receptors (PPAR-γ) and alpha-amylase and further evaluated for in vivo and in vitro antidiabetic, in vitro anti-inflammatory and antioxidant activities. Compound GB14 exhibited significant blood glucose lowering activity and was also found to be active inhibitor of alpha-amylase. Compound GB7 was found to be potent anti-inflammatory agent in terms of reducing inflammatory markers (TNF-α, IL-β, MDA) and also showed antioxidant activity to good extent. Therefore, these compounds may be considered as promising candidates for the development of new antidiabetic agents.
Bansal, Garima,Singh, Shamsher,Monga, Vikramdeep,Thanikachalam, Punniyakoti Veeraveedu,Chawla, Pooja
(2019/09/18)

Novel acetohydrazide pyrazole derivatives: Design, synthesis, characterization and antimicrobial activity
Eleven acetohydrazide linked pyrazole derivatives were designed and synthesized via condensation of acetohyadrazide with different substituted formyl pyrazole derivatives under mild reaction conditions. Synthesized compounds were characterized on the basis of IR, NMR (1H & 13C) and mass spectrometry. The antimicrobial activities of all the compounds were screened against four bacterial and two fungal strains. Among the synthesized compounds, three compounds viz. 6b, 6c and 6d were found as efficient antimicrobial agents in reference to the standard drugs viz. ciprofloxacin and amphotericin-B. Further, structure-activity relationship (SAR) study revealed that electron-withdrawing group enhances the antimicrobial potential of synthesized derivatives as compared to other groups present in the ring. Hence, among compounds 6b-c, compound 6d could be explored further against other microbes to prove its vitality.
Verma, Anil,Kumar, Vinod,Kataria, Ramesh,Singh, Joginder
p. 2740 - 2744
(2019/11/21)

Synthesis, biological evaluation and molecular docking of benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives as novel tubulin polymerization inhibitors
Tubulin-targeting drugs have increasingly become the focus of anticancer drugs research. Twenty-five novel benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives were synthesized and evaluated for bioactivity as potential tubulin polymerization inhibitors. Among them, compound 30 showed the most excellent inhibition against tubulin assembly (IC50 = 1.52 μM) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC50 = 0.15, 0.21, 0.33 and 0.17 μM, respectively for A549, Hela, HepG2 and MCF-7). It could also validly induce A549 cell apoptosis, cause cell cycle arrest in G2/M phase and disrupt the cellular microtubule network. These results, along with molecular docking data, provided an important basis for further optimization of compound 30 as a potential anticancer agent.
Wang, Yan-Ting,Shi, Tian-Qi,Zhu, Hai-Liang,Liu, Chang-Hong
p. 502 - 515
(2019/01/04)

Discovery of novel bacterial FabH inhibitors (Pyrazol-Benzimidazole amide derivatives): Design, synthesis, bioassay, molecular docking and crystal structure determination
The enzyme FabH catalyzes the initial step of fatty acid biosynthesis that is essential for bacterial survival. Therefore, FabH has been identified as an attractive target for the development of new antibacterial agents. We present here the discovery of a
Wang, Yan-Ting,Shi, Tian-Qi,Fu, Jie,Zhu, Hai-Liang
p. 209 - 220
(2019/03/28)

Solubility and solution thermodynamics of novel pyrazolo chalcone derivatives in various solvents from 298.15?K to 328.15?K
Some novel pyrazolo chalcone derivatives have been synthesized and characterization of these synthesized compounds was done by IR, 1H NMR, 13C NMR and mass analysis. The solubility of pyrazolo chalcone derivatives in methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, ethyl acetate and acetonitrile was measured by gravimetric method over a temperature range (298.15 to 328.15) K at atmospheric pressure. The solubility of synthesized compounds is found to increase linearly with temperature. Further, in alcoholic solvents, solubility is maximum in 1-pentanol and minimum in methanol whereas in non-alcoholic solvents, solubility is greater in ethyl acetate and minimum in acetonitrile. The experimental solubility data were correlated with temperature by modified Apelblat and Buchowski-Ksiazczak λh equations. The experimental data and model parameters would be useful for optimizing the process of purification. Some thermodynamic parameters such as dissolution enthalpy, Gibb's free energy and entropy of mixing have also been calculated by Van't Hoff analysis. Further, excess enthalpy of solutions has been calculated using Buchowski-Ksiazczak λh equation.
Baluja, Shipra,Hirapara, Asmita
p. 692 - 704
(2019/01/10)

Pyrazole-pyrazoline as promising novel antimalarial agents: A mechanistic study
A series of pyrazole-pyrazoline substituted with benzenesulfonamide were synthesized and evaluated for their antimalarial activity in vitro and in vivo. The compounds were active against both chloroquine (CQ) sensitive (3D7) and CQ resistant (RKL-9) strains of Plasmodium falciparum. Seven compounds (7e, 7i, 7j, 7l, 7m, 7o and 7p) exhibiting EC50 less than 2 μM. A mechanistic study of compound 7o revealed that these compound act through the inhibition of β-hematin. The study indicated that these compounds can serve as lead compounds for further development of potent antimalarial drugs.
Kumar, Gautam,Tanwar, Omprakash,Kumar, Jitender,Akhter, Mymoona,Sharma, Supriya,Pillai,Alam, Md Mumtaz,Zama
p. 139 - 147
(2018/03/09)

One pot synthesis of thiazolo[2,3-b]dihydropyrimidinone possessing pyrazole moiety and evaluation of their anti-inflammatory and antimicrobial activities
A series of pyrazole integrated thiazolo[2,3-b]dihydropyrimidinone derivatives were synthesized as dual anti-inflammatory and antimicrobial agents. Among the compounds studied, 3-fluoro-4-methylphenyl analogues (3a, 3e, and 3i) are considered to be promising leads for novel anti-inflammatory agents compared with the standard drug. The superior antimicrobial property of the compounds 3a, 3b, and 3d indicates that 3-(3,4-dichlorophenyl)-1-phenyl-1H-pyrazole substitution is a favourable site for high activity. Molecular docking studies were carried out in order to predict the hypothetical binding mode of these compounds to the COX-2 isoenzyme. The results of the present study suggest that 1,3-diaryl pyrazole substitution on thiazolo[2,3-b]dihydropyrimidinone derivatives might potentially constitute a novel class of anti-inflammatory agents with antimicrobial property and could be an interesting approach for the design of new selective COX-2 inhibitory agents.
Viveka, Shivapura,Dinesha,Nagaraja, Gundibasappa Karikannar,Shama, Prasanna,Basavarajaswamy, Guru,Rao, K. Poornachandra,Yanjarappa Sreenivasa, Marikunte
p. 171 - 185
(2018/04/17)

Design, synthesis and cytotoxicity evaluation of pyrazolyl pyrazoline and pyrazolyl aminopyrimidine derivatives as potential anticancer agents
In an attempt to find bio-active heterocyclic analogues, a series of novel 1-(5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-3-(pyridin-3-yl)-4,5-dihydropyrazol-1-yl)ethanones 5a–i and 4-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-6-(pyridine-3-yl)pyrimidin-2-amines 6a–i were designed, synthesized, and evaluated for their in vitro cytotoxicity against a panel of human cancer cell lines namely, HeLa (human cervix), NCI-H460 (human lung), PC-3 (human prostate), and NIH-3T3 (mouse embryo fibroblasts) cell lines. Most of these compounds exhibited moderate to good cytotoxicity against the tested cancer cell lines and weak toxicity against normal cell line. Analogs 5f, 5g, 5i, 6b–g showed significant cytotoxicity as compared to the standard drug etoposide. The compound 6g exhibited superior activity with IC50 value of 5.47 ± 0.44 μM against Hela cancer cell line.
Alam, Raquib,Alam, Aftab,Panda, Amulya K.,Rahisuddin
p. 560 - 570
(2017/10/13)

Thiazolo[3,2-a] Pyrimidones as a Novel Anti-TB Agents
A series of novel thiazolo pyrimidine derivatives were designed, synthesized, and assessed for their in vitro anti-mycobacterial activities. All hybrids displayed considerable antitubercular activities against primary Mycobacterium smegmatis mc2 155 screening and successive Mycobacterium tuberculosis H37Rv. In particular, the hybrid entities 13 and 14 (minimum inhibitory concentration: 47 and 39?μg/mL) were found to be equipotent candidates with first-line antitubercular agent rifampicin, which could act as a lead for further optimization.
Jadhav, Sunil B.,Fatema, Samreen,Bhagat, Sunil S.,Farooqui, Mazahar
p. 2893 - 2900
(2018/10/24)

Synthesis of novel α,α-difluoro-β-hydroxycarbonyl pyrazole derivatives as antioxidant, anti-inflammatory and anticancer agents
A series of novel α,α-difluoro-β-hydroxyl pyrazole esters was prepared by Reformatsky reaction. Subsequently, these esters were converted to acids and hydrazides. All the synthesized compounds were evaluated for their in vitro antioxidant, anti-inflammatory and anticancer potential at various concentrations (50, 100 μM). Compounds 4d and 6e were found to be potent (93.19 and 90.91 %) and compounds 5d, 6c and 5f were good OH radical scavengers (79.55–72.73 %) as compared to the standard drug ascorbic acid (88.63 %). Compounds 6a, 5c, 6f, 4d and 5a showed significant 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (75.95–70.89 %). All the compounds have shown higher cyclooxygenase-1 (COX-1) inhibition over cyclooxygenase-2 (COX-2) at concentrations 100 and 50 μM. Compounds 5f, 6b, 4a, 5c, 4f, 5 and 6d showed significant COX-2 inhibition (38.56–28.30 %) at a concentration of 100 μM compared to standard drug aspirin (11.11 %). Compounds 6f, 6e and 5f have shown significant cytotoxicity against MCF-7 (51.03–40.59 %), whereas 6d, 5f and 5a showed moderate cytotoxicity against HL-60 (26.98–20.21 %) cancer cell lines compared to the methotrexate as reference standard (68.42 and 54.29 % respectively). All compounds have shown almost neglisible cytotoxicity against normal cell line 293.
Mukarram, Salman,Bandgar, Babasaheb P.,Shaikh, Rafik U.,Ganapure, Shriram D.,Chavan, Hemant V.
p. 262 - 273
(2017/01/12)

Design, Synthesis, and Cytotoxicity Evaluation of 3-(5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)pyridine and 5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-3-(pyridin-3-yl)-4,5-dihydropyrazole-1-carbaldehyde Derivatives as Potential Anticancer Agents
In an attempt to find bio-active small molecules, a series of novel 3-(5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)pyridine 5a–i and 5-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-3-(pyridin-3-yl)-4,5-dihydropyrazole-1-carbaldehyde 6a–i were designed, synthesized, and evaluated for their in vitro cytotoxic activity against a panel of human cancer cell lines namely; HeLa (human cervix), NCI-H460 (human lung), PC-3 (human prostate), and NIH-3T3 (mouse embryo fibroblasts) normal cell line. Most of these compounds exhibited moderate to good cytotoxic activity against the tested cancer cell lines and weak toxicity against normal cell line. Analogues 5b, 5f, 5g, 6b, and 6g showed significant cytotoxicity as compared to standard drug etoposide. Among all the synthesized compounds, compound 6g displayed superior cytotoxicity with an IC50 value of 7.98 ± 1.08 μM for Hela cancer cell line.
Alam, Raquib,Alam, Md. Aftab,Panda, Amulya K.,Rahisuddin
p. 1812 - 1821
(2017/05/29)

Design, synthesis, biological evaluation and molecular modelling studies of novel diaryl substituted pyrazolyl thiazolidinediones as potent pancreatic lipase inhibitors
A series of novel diaryl substituted pyrazolyl 2,4-thiazolidinediones were synthesized via reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinedione (TZD) and nitrobenzyl substituted 2,4-thiazolidinedione. The resulting compounds were screened in vitro for pancreatic lipase (PL) inhibitory activity. Two assay protocols were performed viz., methods A and B using p-nitrophenyl butyrate and tributyrin as substrates, respectively. Compound 11e exhibited potent PL inhibitory activity (IC50?=?4.81?μM and Xi50?=?10.01, respectively in method A and B), comparable to that of the standard drug, orlistat (IC50?=?0.99?μM and Xi50?=?3.72). Presence of nitrobenzyl group at N-3 position of TZD and nature of substituent at para position of phenyl ring at C-3 position of pyrazole ring notably affected the PL inhibitory activity of the tested compounds. Enzyme inhibition kinetics of 11e revealed its reversible competitive inhibition, similar to that of orlistat. Molecular docking studies validated the rationale of pharmacophoric design and are in accordance to the in vitro results. Compound 11e exhibited a potential MolDock score of ?153.349?kcal/mol. Further, the diaryl pyrazolyl wing exhibited hydrophobic interactions with the amino acids of the hydrophobic lid domain. Moreover, the carbonyl group at 2nd position of the TZD ring existed adjacent to Ser 152 (≈3??) similar to that of orlistat. A 10?ns molecular dynamics simulation of 11e–PL complex revealed a stable binding conformation of 11e in the active site of PL (Maximum RMSD?≈?3??). The present study identified novel thiazolidinedione based leads with promising PL inhibitory activity. Further development of the leads might result in potent PL inhibitors.
S.N.C., Sridhar,Bhurta, Deendyal,Kantiwal, Dharmvir,George, Ginson,Monga, Vikramdeep,Paul, Atish T.
p. 3749 - 3754
(2017/07/27)

2-(3,4-Dichlorophenylimino)-5-((3-(p-substitutedphenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)thiazolidin-4-one as an Antibacterial, Antifungal and Antimycobacterial Agent
2-(3,4-Dichlorophenylimino)-5-((3-(p-substitutedphenyl)-1-phenyl-1H-pyrazol-4-yl)methylene) thiazolidin-4-one has been selected as a target bio-active molecules. Newly synthesized compounds were screened with Eschericha coli (MTCC 443), Pseudomonas aeruginosa (MTCC 1688), Staphylococcus aureus (MTCC 96), Streptococcus pyogenes (MTCC 442) for antibacterial, Candida albicans (MTCC 227), Aspergillus niger (MTCC 282), Aspergillus clavatus (MTCC 1323) for antifungal activity and H37Rv for antimycobacterial activity. Compounds 3a, 3c, 3d, 3e, and 3h are potentially active against Staphylococcus aureus, while 3h is active against C.?albicans. Compounds 3d and 3f are active against H37Rv for mycobacterium tuberculosis. Other possesses moderate to good activity. The structures of synthesized compounds were firmly established by well-defined elemental analyses (C, H, N, S/O) and spectral analysis technique likes, IR, 1H NMR and GC–MS.
Brahmbhatt, Harshad,Bhatt, Anjani K.,Das, Arun K.,Paul, Parimal,Sharma, Sangita
p. 2838 - 2843
(2017/09/26)

Development of new pyrazole hybrids as antitubercular agents: Synthesis, biological evaluation and molecular docking study
Objective: Synthesis of new 1, 3-diphenyl pyrazole derivatives 9(a-f) and 10(a-f) using molecular hybridization approach and evaluation of their antitubercular and cytotoxic studies. Methods: The structures of synthesized compounds were confirmed by 1H NMR, 13C NMR and mass spectra. The antitubercular activity of compounds and standard drugs were assessed against Mycobacterium tuberculosis using Microplate alamar blue assay (MABA). The cytotoxic activities were performed by Sulforhodamine B (SRB) assay. The molecular docking and in silico ADME prediction studies were also performed by using Schrodinger. Results: The results reveal that compounds 9c, 9d, 10c and 10d exhibited substantial antitubercular potential with MIC10. The molecular docking study was performed to study the binding orientation and affinity of synthesized compounds for InhA enzyme. Conclusion: The study explored that 1, 3-diphenyl pyrazole hybrid coupled with well-known antitubercular drugs could be a potential lead for antitubercular agents. In silico molecular docking, study helps to identify their corresponding intermolecular ligand-protein interactions with target enzyme. Also, ADME prediction studies revealed that the compounds were in acceptable range to have good pharmacokinetic parameters.
Shaikh, Sameer I.,Zaheer, Zahid,Mokale, Santosh N.,Lokwani, Deepak K.
p. 50 - 56
(2017/11/30)

Novel Aryl Substituted Pyrazoles as Small Molecule Inhibitors of Cytochrome P450 CYP121A1: Synthesis and Antimycobacterial Evaluation
Three series of biarylpyrazole imidazole and triazoles are described, which vary in the linker between the biaryl pyrazole and imidazole/triazole group. The imidazole and triazole series with the short -CH2- linker displayed promising antimycobacterial activity, with the imidazole-CH2- series (7) showing low MIC values (6.25-25 μg/mL), which was also influenced by lipophilicity. Extending the linker to -C(O)NH(CH2)2- resulted in a loss of antimycobacterial activity. The binding affinity of the compounds with CYP121A1 was determined by UV-visible optical titrations with KD values of 2.63, 35.6, and 290 μM, respectively, for the tightest binding compounds 7e, 8b, and 13d from their respective series. Both binding affinity assays and docking studies of the CYP121A1 inhibitors suggest type II indirect binding through interstitial water molecules, with key binding residues Thr77, Val78, Val82, Val83, Met86, Ser237, Gln385, and Arg386, comparable with the binding interactions observed with fluconazole and the natural substrate dicyclotyrosine.
Taban, Ismail M.,Elshihawy, Hosam E. A. E.,Torun, Beyza,Zucchini, Benedetta,Williamson, Clare J.,Altuwairigi, Dania,Ngu, Adeline S. T.,McLean, Kirsty J.,Levy, Colin W.,Sood, Sakshi,Marino, Leonardo B.,Munro, Andrew W.,De Carvalho, Luiz Pedro S.,Simons, Claire
p. 10257 - 10267
(2018/01/10)

Design, synthesis and biological evaluation of α-aminophosphonate derivatives containing a pyrazole moiety
Acetylcholinesterase (AChE) is a key enzyme which present in the central nervous system of living organisms. Organophosphorus pesticides (OPs) that serve as insecticides are AChE inhibitors which have been used widely in agriculture. A series of novel OPs containing pyrazole moiety have been designed and synthesized. The biological evaluation indicated compound 4e appeared 81% larvicidal activity against Plutella xylostella at the concentration of 0.1 mg/L and the inhibition of AChE by compound 4e was distinctly enhanced with the increasing doses. Molecular docking of compound 4e into the three dimensional X-ray structure of the Drosophila melanogaster AChE (DmAChE, PDB code: 1QO9) was carried out utilizating the Discovery Studio (DS), the binding model revealed that the title structure was tightly embedded in the binding sites of DmAChE. Therefore, we suggest that compound 4e may serve as a novel AChE inhibitor that can be utilized as a new insecticidal drug.
Ren, Zi-Li,Zhang, Jing,Li, Hai-Dong,Chu, Ming-Jie,Zhang, Li-Song,Yao, Xiao-Kang,Xia, Yong,Lv, Xian-Hai,Cao, Hai-Qun
p. 1755 - 1762
(2016/12/09)

Synthesis of (Z)-1-(1,3-diphenyl-1 H -pyrazol-4-yl)-3-(phenylamino)prop-2-en-1-one derivatives as potential anticancer and apoptosis inducing agents
A series of (Z)-1-(1,3-diphenyl-1H-pyrazol-4-yl)-3-(phenylamino)prop-2-en-1-one derivatives were synthesized and characterized by 1H and 13C NMR, ESI-MS and HRMS. All the synthesized compounds were evaluated for their anticancer activity against HT-29, PC-3, A549 and U87MG human tumor cell lines. Most of the synthesized compounds displayed potent growth inhibition selectively of A549 cancer cells and did not show significant toxicity to the non-cancerous HaCaT cells. Some of the representative compounds, particularly, 16, 22 and 28 exhibited potent growth inhibition with IC50 values in the range of 1.25-3.98 μM, which are comparable or even better than the standard chemotherapeutic drug 5-fluorouracil. Preliminary mechanistic studies revealed that these compounds could effectively inhibit the migration ability of A549 cells. Flow-cytometry analysis revealed that the compounds treatment led to G2/M cell cycle arrest. Moreover, the compounds induced apoptosis in A549 cells through depolarization of mitochondrial membrane potential (DΦm) and increased reactive oxygen species (ROS) production, suggesting their potential to act as promising lead compounds for the development of cancer chemotherapeutics.
Reddy, T. Srinivasa,Reddy, V. Ganga,Kulhari, Hitesh,Shukla, Ravi,Kamal, Ahmed,Bansal, Vipul
p. 157 - 166
(2016/04/26)

Pyrazolylbenzo[d]imidazoles as new potent and selective inhibitors of carbonic anhydrase isoforms hCA IX and XII
Novel pyrazolylbenzo[d]imidazole derivatives (2a-2f) were designed, synthesized and evaluated against four human carbonic anhydrase isoforms belonging to α family comprising of two cytosolic isoforms hCA I and II as well as two transmembrane tumor associated isoforms hCA IX and XII. Starting from these derivatives that showed high potency but low selectivity in favor of tumor associated isoforms hCA IX and XII, we investigated the impact of removing the sulfonamide group. Thus, analogs 3a-3f without sulfonamide moiety were synthesized and biological assay revealed a good activity as well as an excellent selectivity as inhibitors for tumor associated hCA IX and hCA XII and the same was analyzed by molecular docking studies.
Kumar, Satish,Ceruso, Mariangela,Tuccinardi, Tiziano,Supuran, Claudiu T.,Sharma, Pawan K.
p. 2907 - 2913
(2016/06/13)

Design, synthesis and biological evaluation of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1H-pyrazole-4-carboxamides as CDK1/Cdc2 inhibitors
A series of new (N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives (8–35) were designed, synthesized and evaluated as CDK1/Cdc2 inhibitors. Biological evaluation assays indicated that compounds 16 and 27 showed the most potent growth inhibitory activity against human cancer cell lines (MIAPaCa-2, MCF-7 and HeLa) with GI50values ranging from 0.13 to 0.7?μM, compared with the positive control nocodazole (0.81–0.95?μM). Flow cytometric analysis revealed that these compounds induce cell cycle arrest in the G2/M phase and Western blot analysis suggested that compound treatment resulted in reduction of CDK1 expression levels in MCF-7?cell line. Moreover, the apoptosis inducing effect of the compounds was studied using Hoechst staining, Rhodamine 123 staining (MMP), carboxy-DCFDA staining (ROS), Annexin V-FITC assay. Based on these studies, two compounds 16 and 27 have been identified as promising new molecules that have the potential to be developed as leads.
Ganga Reddy,Srinivasa Reddy,Lakshma Nayak,Prasad, Budaganaboyina,Reddy, Adiyala Praveen,Ravikumar,Taj, Shaik,Kamal, Ahmed
p. 164 - 177
(2016/07/06)

Design, synthesis, cytotoxicity, HuTopoIIα inhibitory activity and molecular docking studies of pyrazole derivatives as potential anticancer agents
In an attempt to find potential anticancer agents, a series of novel ethyl 4-(3-(aryl)-1-phenyl-1H-pyrazol-4-yl)-2-oxo-6-(pyridin-3-yl)cyclohex-3-enecarboxylates 5a-i and 5-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-3-(pyridin-3-yl)-4,5-dihydropyrazole-1-carbothioamides 6a-i were designed, synthesized and evaluated for their topoisomerase IIα inhibitory activity and in vitro cytotoxicity against a panel of cancerous cell lines (MCF-7, NCI-H460, HeLa) and a normal cell line (HEK-293T). Molecular docking studies of all the synthesized compounds into the binding site of topoisomerase IIα protein (PDB ID: 1ZXM) were performed to gain a comprehensive understanding into plausible binding modes. These compounds were also screened for in silico drug-likeliness properties on the basis of the absorption, distribution, metabolism and excretion (ADME) prediction. Among all the synthesized compounds, analogue 5d showed superior cytotoxicity with an IC50 value of 7.01?±?0.60?μM for HeLa, 8.55?±?0.35?μM for NCI-H460 and 14.31?±?0.90 for MCF-7 cancer cell lines. Further, compound 5d showed 70.82% inhibition of topoisomerase IIα at a concentration of 100?μM with maximum docking score of ?8.24. Results of ADME prediction revealed that most of these compounds showed in silico drug-likeliness properties within the ideal range.
Alam, Raquib,Wahi, Divya,Singh, Raja,Sinha, Devapriya,Tandon, Vibha,Grover, Abhinav,Rahisuddin
p. 77 - 90
(2016/10/22)

Design, synthesis and cytotoxicity evaluation of novel (E)-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-1-(pyridin-3-yl)prop-2-en-1-ones as anticancer agents
(E)-3-(3-Aryl-1-phenyl-1H-pyrazol-4-yl)-1-(pyridin-3-yl)prop-2-en-1-ones 4a-i have been synthesized and evaluated for their in vitro cytotoxicity against a panel of three human cancer cell lines Caco-2, MIA PaCa-2, MCF-7 and a normal NIH-3T3 cell line. Compound 4g is cytotoxic with the IC50 value of 15.32±0.62 μm against the Caco-2 cell line.
Alam, Raquib,Alam, Md. Aftab,Panda, Amulya K.,Uddin, Rahis
p. 221 - 225
(2016/08/30)

Identification of novel pyrazole-rhodanine hybrid scaffolds as potent inhibitors of aldose reductase: Design, synthesis, biological evaluation and molecular docking analysis
In an effort to develop a new class of potent aldose reductase inhibitors, a series of 1,3-diarylpyrazole assimilated 3-substituted 4-oxo-2-thioxo-1,3-thiazolidines (9a-n) was designed, and synthesized in good to excellent yields by a pharmacophore integr
Andleeb, Hina,Tehseen, Yildiz,Ali Shah, Syed Jawad,Khan, Imtiaz,Iqbal, Jamshed,Hameed, Shahid
p. 77688 - 77700
(2018/06/22)

(E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety as potential immunosuppressive agents: Design, synthesis, molecular docking and biological evaluation
A series of novel (E)-1,3-diphenyl-1H-pyrazole derivatives containing O-benzyl oxime moiety were firstly synthesized and their immunosuppressive activities were evaluated. Among all the compounds, 4n exhibited the most potent inhibitory activity (IC50 Combining double low line 1.18 μM for lymph node cells and IC50 Combining double low line 0.28 μM for PI3Kγ3), which was comparable to that of positive control. Moreover, selected compounds were tested for their inhibitory activities against IL-6 released in ConA-simulated mouse lymph node cells, 4n exhibited the most potent inhibitory ability. Furthermore, in order to study the preliminary mechanism of the compounds with potent inhibitory activity, the RT-PCR experiment was performed to assay the effect of selected compounds on mRNA expression of IL-6. Among them, compound 4n strongly inhibited the expression of IL-6 mRNA.
Lv, Xian-Hai,Li, Qing-Shan,Ren, Zi-Li,Chu, Ming-Jie,Sun, Jian,Zhang, Xin,Xing, Man,Zhu, Hai-Liang,Cao, Hai-Qun
p. 586 - 593
(2015/12/31)

Discovery of N-(benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives as potential antiproliferative agents by inhibiting MEK
Mitogen activated protein kinase (MAPK) signal transduction pathway has been proved to play an important role in tumorigenesis and cancer development. MEK inhibitor has been demonstrated significant clinical benefit for blocking MAPK pathway activation and possibly could block reactivation of the MAPK pathway at the time of BRAF inhibitor resistance. Twenty N-(benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives have been designed and synthesized as MEK inhibitors, and their biological activities were evaluated. Among these compounds, compound 7b showed the most potent inhibitory activity with IC50of 91?nM for MEK1 and GI50value of 0.26?μM for A549 cells. The SAR analysis and docking simulation were performed to provide crucial pharmacophore clues that could be used in further structure optimization.
Lv, Xian-Hai,Ren, Zi-Li,Zhou, Ben-Guo,Li, Qing-Shan,Chu, Ming-Jie,Liu, Dao-Hong,Mo, Kai,Zhang, Li-Song,Yao, Xiao-Kang,Cao, Hai-Qun
p. 4652 - 4659
(2016/09/13)

1,3,4-Trisubstituted pyrazole bearing a 4-(chromen-2-one) thiazole: Synthesis, characterization and its biological studies
A new series 3-{2-[N′-(1,3-disubstituted-1H-pyrazol-4-yl-methylene)-hydrazino]-thiazol-4-yl}-chromen-2-one (10a-l) was synthesized by a multi-step reaction. All the synthesized compounds were characterized by IR, NMR, and mass spectral studies, followed by elemental analysis. The newly synthesized thiazole compounds were screened for their in vitro antibacterial and antifungal studies against various microorganisms. Antimicrobial studies carried out by the well diffusion method, showed a very good zone of inhibition for both bacteria (at a range of 20-50 mm diameter) and fungi (at a range of 10-30 mm diameter). Minimum Inhibitory Concentration (MIC) required for the 100% inhibition of bacteria and fungi was found to be as low as 15.6 μg ml-1 for a few of the synthesized compounds.
Harikrishna,Isloor, Arun M.,Ananda,Obaid, Abdulrahman,Fun, Hoong-Kun
p. 43648 - 43659
(2015/05/27)

Design, synthesis and biological evaluation of 1,3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents
A series of forty different pyrazole containing benzimidazole hybrids (6-45) have been designed, synthesized and evaluated for their potential anti-proliferative activity against three human tumor cell lines - lung (A549), breast (MCF-7), and cervical (HeLa). Some of the compounds, specifically 9, 17, and 28, showed potent growth inhibition against all the cell lines tested, with IC50 values in the range of 0.83-1.81 μM. Breast cancer cells were used for further detailed studies to understand the mechanism of cell growth inhibition and apoptosis inducing effect of compounds. The morphology, cell migration and long term clonogenic survival of MCF-7 breast cancer cells were severely affected by treatment with these compounds. Flow-cytometry revealed the compounds arrested MCF-7 cells in the G1 phase of the cell cycle via down regulation of cyclin D2 and CDK2. Fluorescent staining and DNA fragmentation studies showed that cell proliferation was inhibited by induction of apoptosis. Moreover, the compounds led to collapse of mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) were noted. The ease of synthesis and the remarkable biological activities make these compounds promising new frameworks for the development of cancer therapeutics.
Reddy, T. Srinivasa,Kulhari, Hitesh,Reddy, V. Ganga,Bansal, Vipul,Kamal, Ahmed,Shukla, Ravi
p. 790 - 805
(2015/08/06)

Synthesis and biological evaluation of pyrazolo-triazole hybrids as cytotoxic and apoptosis inducing agents
A series of pyrazolo-triazole hybrids were designed and synthesized by combining the 1,3-diphenyl pyrazole and triazole scaffolds to obtain (1-benzyl-1H-1,2,3-triazol-4-yl)(1,3-diphenyl-1H-pyrazol-4-yl)methanones. All the synthesized compounds were screened for their anticancer activity against four tumor cell lines, viz. HT-29 (colon), PC-3 (prostate), A549 (lung), and U87MG (glioblastoma) cells. Most of the tested compounds showed moderate to potent cell growth inhibition on different cancer cells, in particular, the compounds 17, 23, and 29 exhibited promising cytotoxicity against these cell lines with the IC50 values in the range of 0.86-3.72 μM. In addition, the potential mechanism of cell growth inhibition and apoptotic induction by these compounds was investigated in U87MG cancer cells using cell-based assays, including wound healing assay, flow cytometry, Hoechst staining, acridine orange/ethidium bromide staining, Annexin V-FITC/propidium Iodide dual staining, Rhodamine 123 staining, and carboxy-DCFDA staining. The results indicate that the compounds induce apoptosis in U87MG cells via mitochondrial pathway through up-regulation of pro-apoptotic (Bax) and down-regulation of anti-apoptotic (Bcl-2) genes. Based on these studies, three compounds 17, 23 and 29 have been identified as promising new molecules that have the potential to be developed as leads.
Srinivasa Reddy,Kulhari, Hitesh,Ganga Reddy,Subba Rao,Bansal, Vipul,Kamal, Ahmed,Shukla, Ravi
p. 10136 - 10149
(2015/10/20)

Synthesis and biological evaluation of 1,3-diaryl pyrazole derivatives as potential antibacterial and anti-inflammatory agents
Three series of 1,3-diaryl pyrazole derivatives bearing aminoguanidine or furan-2-carbohydrazide moieties have been synthesized, characterized and evaluated for antibacterial and anti-inflammatory activities. Most of the synthesized compounds showed potent inhibition of several Gram-positive bacterial strains (including multidrug-resistant clinical isolates) and Gram-negative bacterial strains with minimum inhibitory concentration values in the range of 1-64 μg/mL. Compounds 6g, 6l and 7l presented the most potent inhibitory activity against Gram-positive bacteria (e.g. Staphylococcus aureus 4220), Gram-negative bacteria (e.g. Escherichia coli 1924) and the fungus, Candida albicans 7535, with minimum inhibitory concentration values of 1 or 2 μg/mL. Compared with previous studies, these compounds exhibited a broad spectrum of inhibitory activity. Furthermore, compound 7l showed the greatest anti-inflammatory activity (93.59% inhibition, 30 min after intraperitoneal administration), which was more potent than the reference drugs ibuprofen and indomethacin.
Li, Ya-Ru,Li, Chao,Liu, Jia-Chun,Guo, Meng,Zhang, Tian-Yi,Sun, Liang-Peng,Zheng, Chang-Ji,Piao, Hu-Ri
p. 5052 - 5057
(2015/11/09)

Pyrazole clubbed triazolo[1,5-a]pyrimidine hybrids as an anti-tubercular agents: Synthesis, in vitro screening and molecular docking study
A series of novel pyrazole linked triazolo-pyrimidine hybrids were synthesized and evaluated for their anti-tuberculosis activity against M.tb H37Rv strain. Some of the screened entities rendered promising anti-tb activity (MIC: 0.39 μg/mL) and were found non toxic against Vero cells (IC50: ≥20 μg/mL). Further, the docking study against wild type InhA enzyme of Mycobacterium tuberculosis using Glide reproduced the most active inhibitors (J21 and J27) with lowest binding energies and highest Glide XP scores demonstrating efficient binding to the active pocket. Additionally, the enzyme inhibition assay and ADME prediction of the active proved to be an attest to the possibility of developing compound J27 as a potent anti-tubercular lead.
Bhatt, Jaimin D.,Chudasama, Chaitanya J.,Patel, Kanuprasad D.
p. 7711 - 7716
(2015/12/20)

Synthesis, biological evaluation, and molecular docking studies of pyrazolyl-acylhydrazone derivatives as novel anticancer agents
A series of pyrazolyl-acylhydrazone derivatives (1e-20e) have been designed and synthesized and their biologic activities were also evaluated for telomerase inhibition and tumor cell antiproliferation. Among all the compounds, 12e showed the most potent activity in vitro, which inhibited the growth of MCF-7 and B16-F10 cell lines with IC50 values of 0.57 ± 0.03 and 0.49 ± 0.07 μM, respectively. Compound 12e also exhibited significant telomerase inhibitory activity (IC50 = 1.9 ± 0.43 μM). The result of flow cytometry demonstrated that compound 12e induced cell apoptosis. Docking simulation was performed to insert compound 12e into the crystal structure of telomerase at ATP binding site to determine the probable binding model. Based on the preliminary results, compound 12e with potent inhibitory activity in tumor growth may be a potential anticancer agent.
Xing, Man,Zhao, Ting-Ting,Ren, Yu-Jia,Peng, Na-Na,Yang, Xian-Hui,Li, Xi,Zhang, Hui,Liu, Gao-Qi,Zhang, Li-Rong,Zhu, Hai-Liang
p. 3274 - 3286
(2014/06/24)

Synthesis, molecular modeling and biological evaluation of cinnamic acid derivatives with pyrazole moieties as novel anticancer agents
A series of pyrazole derivatives (1e-30e) has been designed and synthesized, and their biological activities were evaluated for EGFR and HER-2 inhibition and tumor cell antiproliferation. Among the compounds synthesized, compound 30e exhibited excellent enzyme inhibitory activity (IC50 = 0.21 ± 0.05 μM for EGFR and IC50 = 1.08 ± 0.15 μM for HER-2). Compound 30e also showed the most potent antiproliferative activity, which inhibited the growth of MCF-7 and B16-F10 cell lines with IC50 values of 0.30 ± 0.04 and 0.44 ± 0.05 μM, respectively. The molecular docking study was performed to analyze the probable binding models and the 3D-QSAR models were built for the rational design of EGFR/HER-2 inhibitors. Based on the results obtained, compound 30e with potent EGFR and HER-2 inhibitory activity may be a potential anticancer agent. the Partner Organisations 2014.
Zhang, Wei-Ming,Xing, Man,Zhao, Ting-Ting,Ren, Yu-Jia,Yang, Xian-Hui,Yang, Yu-Shun,Lv, Peng-Cheng,Zhu, Hai-Liang
p. 37197 - 37207
(2014/12/09)