- Synthesis and biological evaluation of imidazo[2,1-b]thiazole based sulfonyl piperazines as novel carbonic anhydrase ii inhibitors
-
A novel series of imidazo[2,1-b]thiazole-sulfonyl piperazine conjugates (9aa-ee) has been synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory potency against four isoforms: The cytosolic isozyme hCA I, II and trans-membrane tumor-
- Alvala, Mallika,Angeli, Andrea,Manasa, Kesari Lakshmi,Mohammed, Arifuddin,Pujitha, Sravya,Sethi, Aaftaab,Supuran, Claudiu T.
-
-
Read Online
- Synthesis of Combretastatin-A4 Carboxamidest that Mimic Sulfonyl Piperazines by a Molecular Hybridization Approach: in vitro Cytotoxicity Evaluation and Inhibition of Tubulin Polymerization
-
Molecular hybridization approach is a promising structural modification tool to design new chemical entities (NCEs) by mimicking two different pharmacophoric units into one scaffold to enhance the biological properties. With this aim, combretastatin-A4 ac
- Jadala, Chetna,Sathish, Manda,Anchi, Pratibha,Tokala, Ramya,Lakshmi, Uppu Jaya,Reddy, Velma Ganga,Shankaraiah, Nagula,Godugu, Chandraiah,Kamal, Ahmed
-
-
Read Online
- Synthesis of Novel Benzamide- piperazine-sulfonamide Hybrids as Potential Anticancer Agents
-
The synthesis of a series of substituted hippuric acid (2-benzamidoacetic acid) derivatives containing arylsulfonylpiperazine nucleus (3a–j, 4a–j) is described. The compounds were synthesized by coupling hippuric/4-fluorohippuric acid with various arylsulfonylpiperazines using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide (EDCI). The structures of all the new compounds were confirmed by IR, NMR and MS spectral data. All the synthesized compounds have been evaluated for their in vitro cytotoxicity towards five human cancer cell lines of different origins viz. HeLa (Cervical), A549 (Lung), A375 (Skin), MD-AMB-231(Breast) and T98G (brain) and their IC50 values were determined. Among the compounds tested, 3b, 3d, 3g, 4c and 4e displayed significant cytotoxic activity (IC50 = 24.2–38.2 μM). T98G was the most sensitive cell line towards the compounds studied followed by HeLa, A375, A549 and MD-AMB-231.
- Ramalingeswara Rao,Mohana Rao Katiki,Dileep Kommula,SaiShyam Narayanan,Ruby John Anto,Murty
-
-
Read Online
- Discovery of Novel Chromone Derivatives Containing a Sulfonamide Moiety as Anti-ToCV Agents through the Tomato Chlorosis Virus Coat Protein-Oriented Screening Method
-
A number of novel chromone derivatives containing sulfonamide moieties were designed and synthesized, and the activity of compounds against tomato chlorosis virus (ToCV) was assessed using the ToCVCP-oriented screening method. Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models were established based on the dissociation constant (Kd) values of the target compounds, and compound 35 was designed and synthesized with the aid of CoMFA and CoMSIA models. The study of affinity interaction indicated that compound 35 exhibited excellent affinity with ToCVCP with a Kd value of 0.11 μM, which was better than that of the positive control agents xiangcaoliusuobingmi (0.44 μM) and ningnanmycin (0.79 μM). In addition, the in vivo inhibitory effect of compound 35 on the ToCVCP gene was evaluated by the quantitative real-time polymerase chain reaction. ToCVCP gene expression levels of the compound 35 treatment group were reduced by 67.2%, which was better than that of the positive control agent ningnanmycin (59.5%). Therefore, compound 35 can be used as a potential anti-ToCV drug in the future.
- Jiang, Donghao,Chen, Jixiang,Zan, Ningning,Li, Chunyi,Hu, Deyu,Song, Baoan
-
p. 12126 - 12134
(2021/10/26)
-
- Myricetin derivative containing sulfonyl piperazine as well as preparation method and application thereof
-
The invention discloses a myricetin derivative containing sulfonyl piperazine as well as a preparation method and application of the myricetin derivative. The structural general formula of the myricetin derivative is shown in the specification, and n is t
- -
-
Paragraph 0029; 0035-0036; 0069; 0075-0076
(2021/01/24)
-
- Synthesis and antibacterial activity of novel myricetin derivatives containing sulfonylpiperazine
-
Myricetin derivatives containing sulfonylpiperazine were synthesized and their structures were confirmed by NMR and HRMS. The antibacterial activity results indicated that some compounds showed good antibacterial activity against Xanthomonas oryzaepv. ory
- He, Jun,Tang, Xue-Mei,Liu, Ting-Ting,Peng, Feng,Zhou, Qing,Liu, Li-Wei,He, Ming,Xue, Wei
-
p. 1021 - 1027
(2020/10/02)
-
- Design and synthesis of substituted (1-(benzyl)-1: H -1,2,3-triazol-4-yl)(piperazin-1-yl)methanone conjugates: Study on their apoptosis inducing ability and tubulin polymerization inhibition
-
A library of substituted (1-(benzyl)-1H-1,2,3-triazol-4-yl)(piperazin-1-yl)methanone derivatives were designed, synthesized and screened for their in vitro cytotoxic activity against BT-474, HeLa, MCF-7, NCI-H460 and HaCaT cells by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized analogues, compound 10ec displayed the highest cytotoxicity with the IC50 value of 0.99 ± 0.01 μM towards BT-474 cancer cell line. The target compound (10ec) was also evaluated for its tubulin polymerization inhibition study. Detailed biological studies such as acridine orange/ethidium bromide (AO/EB), DAPI and annexin V-FITC/propidium iodide staining assay suggested that compound 10ec induced the apoptosis of BT-474 cells. The clonogenic assay revealed that the inhibition of colony formation in BT-474 cells by 10ec in concentration-dependent manner. Moreover, the flow cytometric analysis revealed that 10ec induced apoptosis via cell cycle arrest at the sub-G1 and G2/M phase. In silico studies of sulfonyl piperazine-integrated triazole conjugates unveil that they possess drug-like properties. According to the molecular modelling studies, compound 10ec binds to the colchicine binding site of the tubulin.
- Alvala, Mallika,Babu, Bathini Nagendra,Devi, Ganthala Parimala,Godugu, Chandraiah,Manasa, Kesari Lakshmi,Nagesh, Narayana,Sigalapalli, Dilep Kumar,Thatikonda, Sowjanya,Vuppaladadium, Sowmya
-
supporting information
p. 1295 - 1302
(2020/12/01)
-
- Design and synthesis of β-carboline linked aryl sulfonyl piperazine derivatives: DNA topoisomerase II inhibition with DNA binding and apoptosis inducing ability
-
A series of new β-carboline linked aryl sulfonyl piperazine congeners have been synthesized by coupling various β-carboline acids with substituted aryl sulfonyl piperazines. Evaluation of their anticancer activity against a panel of human cancer cell lines such as colon (HT-29), breast (MDA-MB-231), bone osteosarcoma (MG-63), brain (U87 MG), prostate (PC- 3) and normal monkey kidney (Vero) cell line has been done. Among the series, compound 8ec and 8ed has shown most potent cytotoxicity with an IC50 values of 2.80 ± 0.10 μM and 0.59 ± 0.28 μM respectively against MG-63 cell line and also potent on other cell lines tested. Compounds 8ec and 8ed was found to inhibit Topo II that is confirmed by specific Topo II inhibition assay. DNA binding studies, cell cycle analysis, Annexin V study indicate that these compounds has potential anticancer activity. Molecular docking studies for compound 8ec and 8ed are incorporated to understand the nature of interaction with topoisomerase IIα and dsDNA.
- Alvala, Mallika,Godugu, Chandraiah,Kalle, Arunasree M.,Kiranmai, Gaddam,Lakshmi Manasa, Kesari,Nagendra Babu, Bathini,Nagesh, Narayana,Sagar, Arpita,Sigalapalli, Dilep Kumar,Thatikonda, Sowjanya
-
-
- Synthesis and biological evaluation of ethacrynic acid derivatives bearing sulfonamides as potent anti-cancer agents
-
A series of ethacrynic acid (2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetic acid) (EA, Edecrin) containing sulfonamides linked via three types of linkers namely 1,2-ethylenediamine, piperazine and 4-aminopiperidine was synthesized and subsequently evaluated in vitro against HL60 and HCT116 cancer cell lines. All the EA analogs, excluding 6a and 6c, showed anti-proliferative activity with IC50s in the micromolar range (less than 4 uM). Three derivatives 6b, 7b and 7e were selected for their interesting dual activity on HL60 cell line in order to be further evaluated against a panel of cancer cell lines (HCT116, A549, MCF7, PC3, U87-MG and SKOV3) as well as on MRC5 as a normal cell line. These compounds displayed IC50 values in nanomolar range against A549, MCF7, PC3 and HCT116 cell lines, deducing the discovery that piperazine or 4-aminopiperidine is the linker's best choice to develop EA analogs with highly potent anti-proliferative activities own up to 24 nM. Besides, in terms of selectivity, those linkers are more suitable offering safety ratios of up to 63.8.
- Bignon, Jér?me,El Abbouchi, Abdelmoula,El Brahmi, Nabil,El Kazzouli, Sa?d,Guillaumet, Gérald,Hiebel, Marie-Aude,Suzenet, Franck
-
supporting information
(2020/08/07)
-
- Sulfonylpiperazines based on a flavone as antioxidant and cytotoxic agents
-
Chrysin-based sulfonylpiperazines 7a-k were synthesized and investigated for their in vitro free radical scavenging potential as well as cytotoxic efficacies against selected cancer cell lines. Cytotoxicity of the new compounds toward noncancer cells was
- Patel, Rahul V.,Mistry, Bhupendra M.,Syed, Riyaz,Parekh, Nikhil M.,Shin, Han-Seung
-
-
- Development of 2-amino-4-phenylthiazole analogues to disrupt myeloid differentiation factor 88 and prevent inflammatory responses in acute lung injury
-
Myeloid differentiation primary response protein 88 (MyD88), an essential adapter protein used by toll-like receptors (TLR), is a promising target molecule for the treatment of respiratory inflammatory diseases. Previous studies explored the activities of novel 2-amino-4-phenylthiazole analogue (6) in inflammation-induced cancer, and identified the analogue as an inhibitor of MyD88 toll/interleukin-1 receptor (TIR) homology domain dimerization. Here, we describe the synthesis of 47 new analogues by modifying different sites on this lead compound and assessed their anti-inflammatory activities in lipopolysaccharide-induced mouse primary peritoneal macrophages (MPMs). The most promising compound, 15d, was found to effectively interact with MyD88 protein and prevented formation of the MyD88 homodimeric complex. Furthermore, 15d showed in vivo anti-inflammatory activity in LPS-caused model of acute lung injury. This work provides new candidates as MyD88 inhibitors to combat inflammation diseases.
- Chen, Lingfeng,Chen, Hongjin,Chen, Pengqin,Zhang, Wenxin,Wu, Chao,Sun, Chuchu,Luo, Wu,Zheng, Lulu,Liu, Zhiguo,Liang, Guang
-
-
- Development of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates bearing sulfonylpiperazine as antitumor inhibitors targeting PI3Kα
-
PI3K signal pathway plays a vital role in cellular functions and becomes an attractive approach for cancer therapy. Herein, a new series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivatives bearing sulfonylpiperazine based on the PI3K inhibitors and our previous research. They were screened for their PI3K inhibitory activities and anticancer effects in vitro. Biological studies indicated that compound 7m revealed the remarkable antiproliferative activity (IC50 ranging from 0.03 to 0.09 μM) against four cancer cell lines (A549, Huh7, HL60 and HCT-116). Besides, compound 7m displayed a certain selective for PI3Kα (IC50 = 0.009 μM) over PI3Kβ, γ and δ, and meanwhile, it can remarkable decreased the expression level of p-Akt (Ser473) and p-S6K. In addition, compound 7m could not only induce HCT-116 cell arrest at G1 phase in a dose-dependent manner, but also induce cell apoptosis via upregulation of Bax and cleaved-caspase 3/9, and downregulation of Bcl-2. Besides, compound 7m can remarkably inhibit the growth of tumor in vivo. The above results suggested that compound 7m could be considered as a promising PI3Kα inhibitor.
- Yin, Yong,Sha, Shao,Wu, Xun,Wang, She-Feng,Qiao, Fang,Song, Zhong-Cheng,Zhu, Hai-Liang
-
-
- Tankyrase inhibitor
-
The invention belongs to the technical field of medicines and particularly relates to a tankyrase inhibitor represented by a general formula (I) shown in the description and pharmaceutically acceptable salts, esters, solvates or stereoisomers thereof, wherein R1, R2, R3, m, n, Z, L, Q, A, X1, X2 and Y are as defined in the description. The invention further relates to a preparation method for the compounds, pharmaceutical preparations and pharmaceutical compositions containing the compounds and application of the compound and the pharmaceutically acceptable salts, esters, solvates or stereoisomers thereof in preparation of drugs for treating and/or preventing tankyrase mediated cancers and related diseases.
- -
-
-
- HEPATITIS B VIRAL ASSEMBLY EFFECTORS
-
Novel assembly effector compounds having a therapeutic effect against hepatitis B viral (HBV) infection are disclosed. Assembly effector molecules described herein can lead to defective viral assembly and also may affect other viral activities associated with chronic HBV infection. Also disclosed is a process to synthesize disclosed compounds, method of treatment of HBV by administration of disclosed compounds, and use of these compounds in the manufacture of medicaments against HBV.
- -
-
-
- Solution-phase parallel synthesis and SAR of homopiperazinyl analogs as positive allosteric modulators of mGlu4
-
Using a functional high-throughput screening (HTS) and subsequent solution-phase parallel synthesis approach, we have discovered a novel series of positive allosteric modulators formGlu4, a G-protein coupled receptor. This series is comprised of a homopiperazine central core. The solution-phase parallel synthesis and SAR of analogs derived from this series will be presented. This series of positive allosteric modulators of mGlu4 provide critical research tools to further probe the mGlu4-mediated effects in Parkinson's disease.
- Cheung, Yiu-Yin,Zamorano, Rocio,Blobaum, Anna L.,Weaver, C. David,Conn, P. Jeffrey,Lindsley, Craig W.,Niswender, Colleen M.,Hopkins, Corey R.
-
p. 159 - 165
(2011/06/19)
-
- Structure-activity relationship studies of sulfonylpiperazine analogues as novel negative allosteric modulators of human neuronal nicotinic receptors
-
Neuronal nicotinic receptors have been implicated in several diseases and disorders such as autism, Alzheimer's disease, Parkinson's disease, epilepsy, and various forms of addiction. To understand the role of nicotinic receptors in these conditions, it would be beneficial to have selective molecules that target specific nicotinic receptors in vitro and in vivo. Our laboratory has previously identified novel negative allosteric modulators of human α4β2 (Hα4β2) and human α3β4 (Hα3β4) nicotinic receptors. The effects of novel sulfonylpiperazine analogues that act as negative allosteric modulators on both Hα4β2 nAChRs and Hα3β4 nAChRs were investigated. This work, through structure-activity relationship (SAR) studies, describes the chemical features of these molecules that are important for both potency and selectivity on Hα4β2 nAChRs. (Figure presented)
- Henderson, Brandon J.,Carper, Daniel J.,González-Cestari, Tatiana F.,Yi, Bitna,Mahasenan, Kiran,Pavlovicz, Ryan E.,Dalefield, Martin L.,Coleman, Robert S.,Li, Chenglong,McKay, Dennis B.
-
supporting information; experimental part
p. 8681 - 8692
(2012/02/15)
-
- N-SULFONYL THIAZOLYLPIPERAZINE DERIVATIVES AND RELATED N-SULFONYL HETEROCYCLIC DERIVATIVES FOR THE TREATMENT OF NEURO DEGENERATIVE DISEASES
-
This invention provides thiazolylpiperazine derivatives, and N-sulfonyl heterocyclic derivatives including phenyl- and benzyl-thiazolylpiperidine derivatives, and pharmaceutically acceptable salts thereof, which are useful active ingredients for administration in a method for the treatment of an α-synucleopathy such as Parkinson's disease, diffuse Lewy body disease, traumatic brain injury, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy and Alzheimer's disease. This invention also provides methods for making such derivatives, and pharmaceutical compositions including such derivatives together with pharmaceutically acceptable excipients.
- -
-
Page/Page column 80-81; sheet 3
(2010/08/08)
-
- BETA-3 RECEPTOR LIGANDS AND THEIR USE IN THERAPY
-
The present invention relates to new compounds, ligands of the beta-3 adrenergic receptor, their preparation and their use in therapy or as research tools for said receptor; the invention also relates to a process for the preparation of the compounds of the invention and the use of inverse agonists of the beta-3 adrenergic receptor as medicaments.
- -
-
Page/Page column 11
(2010/04/23)
-
- Effect of Amine Nature on Reaction Rate and Mechanism in Nucleophilic Substitution Reactions of 2,4-Dinitrophenyl X-Substituted Benzenesulfonates with Alicyclic Secondary Amines
-
Second-order rate constants have been measured for reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates with a series of alicyclic secondary amines. The reaction proceeds through S-O and C-O bond fission pathways competitively. The S-O bond fission occurs more dominantly as the amine basicity increases and the substituent X in the sulfonyl moiety becomes more strongly electron withdrawing, indicating that the regioselectivity is governed by the amine basicity as well as the electronic nature of the substituent X. The S-O bond fission proceeds through an addition intermediate with a change in the rate-determining step at pKa° = 9.1. The secondary amines are more reactive than primary amines of similar basicity for the S-O bond fission. The k1 value has been determined to be larger for reactions with secondary amines than with primary amines of similar basicity, which fully accounts for their higher reactivity. The second-order rate constants for the S-O bond fission result in linear Yukawa-Tsuno plots while those for the C-O bond fission exhibit poor correlation with the electronic nature of the substituent X. The distance effect and the nature of reaction mechanism have been suggested to be responsible for the poor correlation for the C-O bond fission pathway.
- Um, Ik-Hwan,Chun, Sun-Mee,Chae, Ok-Mi,Fujio, Mizue,Tsuno, Yuho
-
p. 3166 - 3172
(2007/10/03)
-
- Pharmacological exploitation of the alpha1-adrenoreceptor antagonist doxazosin to develop a novel class of antitumor agents that block intracellular protein kinase B/Akt activation.
-
The alpha1-adrenoreceptor antagonist doxazosin induces apoptosis in malignant cells with moderate potency via an alpha1-adrenoreceptor-independent mechanism. Here, we demonstrate that the ability of doxazosin to induce apoptosis in PC-3 prostate cancer cells was, in part, attributable to the inhibition of protein kinase B (PKB)/Akt activation. The separation of the effect of doxazosin on apoptosis from its original pharmacological activity provides molecular underpinnings to develop novel antitumor agents. Replacement of the (2,3-dihydro-benzo[1,4]dioxane)-carbonyl moiety of doxazosin with aryl-sulfonyl functions dramatically improves the potency in facilitating Akt deactivation and inducing apoptosis. The optimal compounds, 33 and 44, were effective in apoptosis induction at low micromolar concentrations irrespective of androgen dependency and p53 functional status. Both agents were active in suppressing the growth of a panel of 60 cancer-cell lines with IC50 values of 2.2 and 1.5 microM, respectively. Together, these in vitro efficacy data suggest the translational potential of these agents in prostate cancer treatment.
- Shaw, Yeng-Jeng,Yang, Ya-Ting,Garrison, Jason B,Kyprianou, Natasha,Chen, Ching-Shih
-
p. 4453 - 4462
(2007/10/03)
-