- Aldoxime- and hydroxy-functionalized chalcones as highly potent and selective monoamine oxidase-B inhibitors
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A panel of 30 chalcone derivatives, including 19 aldoxime-chalcone ethers (ACE), and 11 hydroxyl?chalcones (HC), previously synthesized using a Pd-catalyzed C–O cross-coupling method were evaluated for their inhibitory activities against monoamine oxidases (MAOs), cholinesterases (ChEs), and β-secretase (BACE-1). HC6 was the most potent inhibitor of MAO-B with an IC50 value of 0.0046 μM and a selectivity index (SI) of 1,113. HC3 also potently inhibited MAO-B (IC50 = 0.0067 μM) and had the highest SI (1,455). ACE7 and ACE15 were also potent MAO-B inhibitors (IC50 = 0.012 and 0.018 μM, respectively), with SIs of 260 and 1,161, respectively. HC3 and HC6 were reversible competitive inhibitors of MAO-B, with Ki values of 0.0036 and 0.0013 μM, respectively. A structure–activity relationship revealed that methyl and fluorine substituents contributed to increasing both inhibition and selectivity. ACE7 was the most effective inhibitor of MAO-A (IC50 = 1.49 μM), followed by ACE3 (IC50 = 3.75 μM). No compounds effectively inhibited AChE, BChE, or BACE-1. A docking simulation showed that the ligand efficiency and docking scores of HC3 and HC6 toward MAO-B were consistent with the experimental IC50 values. These results suggest that HC3 and HC6 can be considered promising candidates for the treatment of neurological disorders.
- Oh, Jong Min,Rangarajan,Chaudhary, Reeta,Gambacorta, Nicola,Nicolotti, Orazio,Kumar, Sunil,Mathew, Bijo,Kim, Hoon
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- Antibacterial and anti-inflammatory activity of valproic acid-pyrazole conjugates as a potential agent against periodontitis
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Periodontitis is a serious global concern. Therefore, in the present study, we intend to synthesize novel valproic-acid pyrazole conjugates as a novel agent against periodontitis. The molecules were developed in a facile synthetic route and obtained in ex
- Dai, Xinxiang,Dong, Lei,Fang, Ling,Wang, Jia,Xu, Pei,Zhang, Jia
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- Structure-activity relationship with pyrazoline-based aromatic sulfamates as carbonic anhydrase isoforms I, II, IX and XII inhibitors: Synthesis and biological evaluation
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Four new series of aromatic sulfamates were synthesized and investigated for the inhibition of four human (h) isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), hCA I, II, IX, and XII. The reported derivatives, obtained by a sulfamoylation reaction of the corresponding phenolic precursors, bear 3,5-diarylpyrazoline moieties as spacers between the benzenesulfamate fragment which binds the zinc ion from the active site, and the tail of the inhibitor. Pyrazolines are biologically privileged scaffolds, endowed with versatile biological activity, such as an anti-proliferative action. The derivatives were tested for the inhibition of the cytosolic, hCA I and II (off target isoforms) and the trans-membrane, tumor-associated hCA IX and XII enzymes (anticancer drug targets). Generally, hCA I was not effectively inhibited, whereas many low nanomolar inhibitors were evidenced against hCA II (KIs in the range of 0.42–90.1 nM), IX (KIs in the range of 0.72–63.6 nM), and XII (KIs in the range of 0.88–85.2 nM). The best substitution fragments at the pyrazoline ring included for CA II a 4-sulfamic group on the 3-aryl and halogens on the 5-aryl or a methoxy group on the 3-aryl and a 4-sulfamate group on the 5-aryl; for CA IX and CA XII they included the sulfamic group on the 3- or 4-position of the 5-aryl and an electronwithdrawing group on the 4-postion of the 3-aryl ring.
- Moi, Davide,Nocentini, Alessio,Deplano, Alessandro,Balboni, Gianfranco,Supuran, Claudiu T.,Onnis, Valentina
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- NOTCH INHIBITORS FOR USE IN THE TREATMENT OF T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
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Compounds of formula (I) in the capacity of compounds with anti-tumor activity for the treatment of T-cell acute lymphoblastic leukemia (T-ALL).
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Page/Page column 25-26; 39-40
(2018/07/29)
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- Design, synthesis and bioactivity of chalcones and its analogues
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The Vernohia anthelmintica L.'s extract is one of the most popular Uygur medicines used for vitiligo. It is believed that the chalcone compounds of the plant play an important role in the treatment since they may activate tyrosinase and improve melanin production. In this study, twenty-one chalcones and nine analogues were synthesized in view of three different components of chalcone (A, B ring and α, β-unsaturated carbonyl). After biological evaluation of their activity on tyrosinase in cell-free systems, the result showed that most compounds (except polyhydroxy chalcones) possess activator effect on the tyrosinase, especially for 13a–15a, 20a and 1b, which bearing a comparable activity to the positive control 8-MOP. SAR of these tyrosinase activator was summed up for the first time as well. Finally, compound 13a was found to increase melanin contents and tyrosinase activity 1.75 and 1.3 fold, respectively, compared with that of untreated murine B16 cells at the concentration of 40?μg/mL.
- Niu, Chao,Tuerxuntayi, Adila,Li, Gen,Kabas, Madina,Dong, Chang-Zhi,Aisa, Haji Akber
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supporting information
p. 1533 - 1538
(2017/07/17)
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- 2-pyrazoline derivatives in neuropharmacology: Synthesis, adme prediction, molecular docking and in vivo biological evaluation
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A novel series of 1,3,5-trisubstituted-2-pyrazoline derivatives (PFC-1 to PFC-16) were synthesized in a three step reaction using conventional and microwave assisted green chemistry approach. The synthesized derivatives were characterized and their chemic
- Upadhyay, Savita,Tripathi, Avinash C.,Paliwal, Sarvesh,Saraf, Shailendra K.
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p. 628 - 649
(2017/06/05)
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- Microwave-assisted synthesis and bioevaluation of new sulfonamides
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In this study, 4-[5-(4-hydroxyphenyl)-3-aryl-4,5-dihydro-1H-pyrazol-1-yl]benzenesulfonamide derivatives (8-14) were synthesized for the first time by microwave irradiation and their chemical structures were confirmed by 1H NMR, 13C N
- Gul, Halise Inci,Yamali, Cem,Yesilyurt, Fatma,Sakagami, Hiroshi,Kucukoglu, Kaan,Gulcin, Ilhami,Gul, Mustafa,Supuran, Claudiu T.
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p. 369 - 374
(2017/11/10)
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- Synthesis, in Vitro, and in Vivo Biological Evaluation and Molecular Docking Analysis of Novel 3-(3-oxo-substitutedphenyl-3-)4-(2-(piperidinyl)ethoxy)phenyl)propyl)-2H-chromen-2-one Derivatives as Anti-breast Cancer Agents
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The analogs of coumarin-chalcones have been reported to exhibit antineoplastic, anti-allergic, antihepatoprotective, and estrogenic activity. Herein, we have reported 3-(3-oxo-substitutedphenyl-3-)4-(2-(piperidinyl)ethoxy)phenyl)propyl)-2H-chromen-2-one derivatives as a new class of compounds that exhibit selectivity for ER-α binding along with antiproliferative and cytotoxic activity on human breast cancer cell line. The active compounds which show prominent activity against estrogen receptor-alpha-positive (ER+) human breast cancer cell lines MCF-7 and Zr-75-1 are subjected to in vivo screening. The Glide XP docking was performed for designed scaffold to optimize its structural requirement for ER-α inhibition.
- Dube, Pritam N.,Waghmare, Madhuri N.,Mokale, Santosh N.
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p. 608 - 617
(2016/03/19)
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- Mesomorphism of azo-esters and chalcone-esters
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AOne chalcone-ester homologous series of mesogens α-4-[4/-n-alkoxybenzoyloxy phenyl β-4//methoxy benzoyl ethylenes (A) and one azo-ester homologous series of mesogens p-(p/-n-alkoxybenzoyloxy) phenyl azo-p//-methoxy benzene (B) being structurally similar are discussed. Both series (A) and (B) differ in respect of central bridges linking two phenyl rings. Mesomorphic properties start from 6th and 1st member of series (A) and (B) respectively. In series (A), 6th to 12th members show both smectogenic and nematogenic properties, and the 14th and 16th members show only nematogenic property. While in series (B), 1st to 10th members show nematogenic properties, 11th member shows both smectogenic and nematogenic properties, while 12th member shows only smectogenic property. Thermal stability of series (A) is relatively high as compared to series (B). Transition temperatures are observed through hot stage polarizing microscope by the miscibility method. Analytical data support the structure of molecules. Textures of series (A) in nematic are threaded and Schlieren in SmecticSmectic A type, while that of series (B) in nematic are threaded in SmecticSmectic A and smectic C.
- Jain,Sharma, Vinay S.,Chauhan,Patel
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p. 102 - 111
(2016/07/14)
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- Synthesis of some novel 5,7-disubstituted-2-phenyl-5H-[1,3,4]thiadiazolo [3,2-a]pyrimidine derivatives and evaluation of their biological activity
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Background: In the present study, a series of 5,7-disubstituted-2-phenyl-5H-[1,3,4] thiadiazolo[3,2-a]pyrimidine derivatives have been reported. The title compounds were synthesized by the reaction of substituted chalcones with 5-phenyl-1,3,4-thiadiazol-2-amine in n-butanol. Methods: All reactions were performed at reflux temperature and the synthesized compounds were characterized by IR, NMR and Mass spectroscopic techniques. Results: The synthesized compounds were screened for their antimicrobial and antioxidant activities. The compounds displayed significant antimicrobial and antioxidant activities. Additionally, the selected compounds were screened for in silico molecular docking studies. Conclusion: In the present work, we have reported an efficient method for the synthesis of some new 5,7-disubstituted-2-phenyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidine derivatives. Collectively, all the current computational insights support the in vitro observations seen for antimicrobial and antioxidant agents. Further, the pyrimidine derivatives might act as potential specific inhibitors of G6P synthase thereby facilitating its biological activities. From the activity results, it has been concluded that among the studied compounds, compounds 5b, 5d, 5e, 5g, 5i, 5m and 5n could serve as potential antimicrobial and antioxidant agents.
- Venkatesh, Talavara,Bodke, Yadav D.,Joy, Nibin M.,Vinoda,Shiralgi, Yallappa,Dhananjaya
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p. 661 - 671
(2017/01/13)
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- Niacin esters of chalcones with tumor-selective properties
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Novel series of niacin esters of chalcones 2, 4 and 6 were designed as antineoplastic agents that have the potential to release the chemoprotectant niacin. These enones are cytotoxic to human CD4 +T-lymphocyte Molt 4/C8 and CEM and murine leukemia L1210 cells. Quantitative structure–activity relationship (QSAR) studies of the biodata in series 4 revealed that cytotoxic potency was enhanced by placing electron-repelling groups in one of the aryl rings. The compounds are lethal to HL-60, HSC-2, HSC-3 and HSC-4 neoplasms but less toxic to nonmalignant hepatocyte growth factor, hematopoietic progenitor cell and human periodontal ligament fibroblast cells. Hence, the compounds display tumor-selective toxicity. These chalcones are well tolerated in mice and no overt toxicity was noted. The results establish that in general the compounds in series 2, 4 and 6 have positive characteristics which warrant further studies.
- Panda, Atulya K.,Das, Umashankar,Roayapalley, Praveen K.,Sakagami, Hiroshi,Kawase, Masami,Balzarini, Jan,De Clercq, Erik,Dimmock, Jonathan R.
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p. 1451 - 1456
(2016/10/09)
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- Highly efficient deprotection of phenolic tetrahydropyranyl and methoxymethyl ethers and sequel cyclization to indanones using Sn(IV)Cl 4 catalyst
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Sn(IV)Cl4 catalyst provided a rapid and efficient deprotection method for the phenolic THP and MOM ethers and sequel intramolecular Friedel-Crafts alkylation reaction of THP and MOM protected chalcone epoxides under mild conditions. The reaction took 2-3 min to give the products in excellent yield (90-98%) at 0 °C without affecting the other functional groups.
- Ahmed, Naseem,Pathe, Gulab Khushalrao,Venkata Babu
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supporting information
p. 3683 - 3687
(2014/06/23)
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- A novel homologous series of thermotropic mesogens of ethylene derivatives: α-4-[4′-n-Alkoxy Benzoyloxy] phenyl β-4″ methoxy benzoyl ethylenes
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A novel homologous series consists of 12 compounds. The shorter chain homologues do not show liquid crystal phases, but from six carbons onwards, the nematic phase is exhibited enantiotropically, with some members also showing a smectic phase. The phase behavior of the transition curves of the series shows a usual trend. The texture of the nematic phase is the threaded or Schlieren type and that of smectic phase is a smectic A. An odd-even effect is observed for smectic-nematic and nematic-isotropic transition curves. Analytical data confirm the molecular structure. The transition temperatures were determined by an optical polarizing microscopy. The mesogenic properties of the novel series are compared with a structurally similar homologous series. The average smectic-nematic and nematic-isotropic thermal stabilities are 133.4°C and 159.8°C, respectively, with a mesogenic temperature range of 10°C to 62°C.
- Chauhan,Doshi
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- Inhibitory effect of curcumin analogs on tissue factor procoagulant activity and their preliminary structure-activity relationships
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With the aim to explore the multifunctional behaviors of curcumin analogs and to discover new small molecular tissue factor inhibitors, twelve mono carbonyl curcumin analogs of three classes were synthesized and their effect on tissue factor procoagulant activity was evaluated in the human monoblastic leukemia THP-1 cells stimulated by LPS. The most potent compounds 2a exhibited the dramatically enhanced activity with the IC50 values of 0.053 nM. Their preliminary structure-activity relationship was also discussed.
- Ge, Hai-Xia,Chen, Ling,Zhang, Jian,Kou, Jun-Ping,Yu, Bo-Yang
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p. 3242 - 3246
(2013/07/27)
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- Synthesis and study of antibacterial activity of some 1-phenyl-3-aryl-5-(4- (2-ethanoloxy) phenyl)-1H-pyrazoles
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A series of 1-phenyl-3-aryl-5-(4-(2-ethanoloxy) phenyl)-1H-pyrazoles were synthesized from chalcones and studied for their in vitro antibacterial activity. Chalcones i.e., 1-aryl-3-(4-hydroxyphenyl) prop-2-en-1-ones, 1 on reaction with phenyl hydrazine yi
- Goyal, Anju,Jain, Neelam,Jain, Sandeep
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p. 553 - 558
(2013/11/06)
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- Synthesis and antitumor activity of 1-acetyl-3-(4-phenyl)-4,5-dihydro-2- pyrazoline-5-phenylursolate and 4-chalcone ursolate derivatives
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New 4-chalcone ursolate and 1-acetyl-3-(4-phenyl)-4,5-dihydro-2-pyrazoline- 5-phenyl ursolate derivatives were synthesized by esterification of UA and chalcone or pyrazoline. The compounds were structurally confirmed by IR, 1H NMR, 13/sup
- Bai, Xue,Shi, Wan Qi,Chen, Hua Feng,Zhang, Ping,Li, Ying,Yin, Shu Fan
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experimental part
p. 60 - 65
(2012/08/07)
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- Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives as EGFR TK inhibitors and potential anticancer agents
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Fourty-two thiazolyl-pyrazoline derivatives were synthesized to screen for their EGFR kinase inhibitory activity. Compound 4-(4-chlorophenyl)-2-(3-(3,4- dimethylphenyl)-5-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazole (11) displayed the most potent EGFR TK inhibitory activity with IC50 of 0.06 μM, which was comparable to the positive control. Molecular docking results indicated that compound 11 was nicely bound to the EGFR kinase. Compound 11 also showed significant antiproliferative activity against MCF-7 with IC 50 of 0.07 μM, which would be a potential anticancer agent.
- Lv, Peng-Cheng,Li, Dong-Dong,Li, Qing-Shan,Lu, Xiang,Xiao, Zhu-Ping,Zhu, Hai-Liang
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scheme or table
p. 5374 - 5377
(2011/10/12)
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- Efficient synthesis of chalcone derivatives catalyzed by re-usable hydroxyapatite
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Hydroxyapatite was found to be a very efficient heterogeneous catalyst for the preparation of chalcone derivatives via Claisen-Schmidt condensation using microwave irradiation. The impact of water on the catalyst reactivity was studied and was thought to act as co-catalyst due to the high activation observed in its presence. To investigate the origin of this activation, different organic solvents of similar or higher microwave absorbance as/to water were also tested, and it was confirmed that water is acting as co-catalyst when combined with hydroxyapatite, making the process highly efficient. The catalyst was easily recovered and efficiently re-used.
- Solhy,Tahir,Sebti,Skouta,Bousmina,Zahouily,Larzek
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experimental part
p. 189 - 193
(2010/11/04)
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- Synthesis and photoinduced reorientation of polymethacrylates comprising photocrosslinkable phenylbenzoate mesogenic side groups
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This paper describes synthesis and photoreaction of photocrosslinkable liquid crystalline (LC) polymethacrylates comprising phenyl benzoate mesogenic side groups attached with a photoreactive end group. All synthesized polymers exhibited a nematic LC natu
- Kawatsuki, Nobuhiro,Kitani, Yuki,Oda, Akihiro
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p. 153 - 161
(2007/10/03)
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