A B C D E F G H I J K L M N O P Q R S T U V W X Y Z All
Choudhari, Prafulla B.
- K Nearest Neighbor and 3D QSAR Analysis of Thiazolidinone Derivatives as Antitubercular Agents
Authors
1 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, Maharashtra, IN
2 Department of Pharmaceutics, Ashokrao Mane College of Pharmacy, Peth Vadgaon, Maharashtra, IN
Source
Journal of Pharmaceutical Research, Vol 15, No 3 (2016), Pagination: 67-72Abstract
Purpose: The present research communication describes development of kNN and 3D QSAR models for identification of structural features which are responsible for antimycobacterial activity of Thiazolidinone.
Methodology/Approach : In the present work, two predictiveof kNN and 3D QSAR models were developed via utilization of multiple linear regression analysis. MLR analysis was carried out on reported dataset of thiazolidinone as Antimycobacterial. Vlife MDS 4.4 is utilized for development of kNN and 3D QSAR models which were validated via internal test set.
Findings : Two different kNN and 3D QSAR models developed for dataset of thiazolidinone molecules as antimycobacterial. The Model A and Model B describes the best selected 3D QSAR model predicting antimycobacterial activity of the thiazolidinone derivatives. 3D QSAR model A is best selected model which indicates steric interaction fields needs to be minimized while electrostatic interaction field needs to be improved for potential increase in antimycobacterial activity. The Model C and D are two selected kNN models for anti-mycobacterial activity of the thiazolidinone derivatives. Model D is better fitted kNN model describing negative contribution of the electrostatic interaction fields and positive contribution of the steric interaction field.
Original Value : The review of literature revealed QSAR analysis plays vital role in the development of the novel drug like candidates. Thiazolidinone derivatives were reported for their antimycobacterial potential but their quantitative measures were not reported. These facts prompted us to for development of QSAR models which will be utilized for development of potent and selective antimycobacterial agents.
Conclusion : The study revealed that 3DQSAR model A and kNN model D better describes the antimycobacterial potential of the thiazolidinone derivatives. Substitution of the smaller groups on the aromatic ring bearing thiazolidinone nucleus will increase the antimycobacterial potential of the thiazolidinone derivatives.
Keywords
Thiazolidinone Derivatives, Antimycobacterial, 3D QSAR, kNN-MFA.References
- Lou Z, Zhang X. Protein targets for structure-based antiMycobacterium tuberculosis drug discovery. Protein Cell.2010;1(5):435–42.
- Chopra P, Meena LS, Singh Y. New drug targets for Mycobacterium tuberculosis. Indian J Med Res. 2003; 117:1-9.
- Kamal Ahmed, Azeeza A, Malik MS, Shaik AA, Rao MV. Efforts Towards the Development of New Antitubercular Agents: Potential for Thiolactomycin Based Compounds J Pharm Pharmaceut Sci.2008;11 (2):56-80.
- Mdluli K, Spigelman M. Novel targets for tuberculosis drug discovery CurrOpi-Pharmaco.2006;6:459–467.
- Sharma MC, Sharma S, Sahu NK, Kohli DV. 3D QSAR kNN-MFA studies on 6-substituted benzimidazoles derivatives as Nonpeptide Angiotensin II Receptor Antagonists: A rational approach to antihypertensive agents.J SauChemSoc.2013;17:167–76.
- Sharma MC. Structural requirements of N-aryloxazolidinone5-carboxamide derivatives for anti-HIV protease activity using molecular modelling techniques.J Tai Uni Sci.2014;8:111–23.
- Choudhari PB, Bhatia MS.3D QSAR, pharmacophore identification studies on series of 1-(2-ethoxyethyl)-1hpyrazolo [4,3-d]pyrimidines as phosphodiesterase V inhibitors J SauChemSoc.2015;19(3):265–73.
- Desai SA, Kumbhar SS, Katti VS, Choudhari PB, Bhatia M. S. 3D QSAR and Pharmacophore Modelling on Chalcones as Antileishmanial Agents potential Trypanothionereductase Inhibitors. JAppPharma Sci. 2013;3: 99-02.
- Choudhari PB, Bhatia MS, Bhatia NM. Application of pocket modeling and k nearest neighbour molecular field analysis (kNN-MFA) for designing of some anticoagulants: potential factor IXa inhibitors. Med Chem Res.2013;22:976-85.
- Malipeddi H, Karigar AA, Malipeddi VR, Sikarwar MS. Synthesis and Antitubercular Activity of Some Novel Thiazolidinone Derivatives. TroJ of Pharm Res. 2012; 11 (4):611-20.
- Exploration of Anticancer Potential of Spiropyranopyrazole Derivatives as CDK7 Inhibitors
Authors
1 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Near Chitranagari, Kolhapur - 416 013, Maharashtra, IN
2 Department of Pharmacology, Appasaheb Birnale College of Pharmacy, Sangli, Maharashtra, IN
3 Department of Chemistry, Shivaji University, Vidyanagar, Kolhapur, Maharashtra, IN
Source
Journal of Pharmaceutical Research, Vol 15, No 3 (2016), Pagination: 73-78Abstract
Purpose : The Spiropyranopyrazole derivatives are used as cytotoxic agents and nitrogen containing heterocyclic analogs targeting CDK7 inhibition shows better cytotoxic activity.
Methodology: A new series of compounds were synthesized using various substituted isatin derivatives and then characterized and analyzed for biological activity by in-silico and using MTT assay targeting CDK7. All the synthesized compounds were analyzed for their biological activity for this purpose breast cancer cell lines (MCF7) were used and analyzed by MTT assay. Docking studies into ATP binding site of CDK7 were performed to predict their binding affinity scores and possible interactions with receptor to evaluate bioactivity in-silico using VLife MDS 4.3.
Findings : A novel series of Spiropyranopyrazole derivatives were successfully synthesized via Multicomponent reaction (MCR). From experimental data indicated that compounds 2c and 3c showed most promising results as their inhibitory activity with 23.20% and 26.50% respectively at 10μM and these were selected for further preclinical studies.
Social Implications : If the present findings of spiropyranopyrazole derivatives passes preclinical studies and we develop drug like candidate then it is a massive achievement in anticancer therapy that could save many lives.
Original : Successfully develop a novel series of spiropyranopyrazole having CDK7 inhibitor activity. This could be helpful for development of a drug like candidate having significant cytotoxic activity.
Keywords
Cell Cycle, CDK7, Isatin, Spiropyranopyrazole Derivatives, Anticancer, VLife MDS 4.3.References
- Sun J, Lv X, Qiu H, Wang Y, Du Q, Li D, Yang Y, Zhu H. Synthesis, biological evaluation and molecular docking studies of pyrazole derivatives coupling with a thiourea moiety as novel CDKs inhibitors. Eur J Med Chem. 2013; 68:1-9.
- Diallo A, Prigent C. The serine/threonine kinases that control cell cycle progression as therapeutic targets. Bull Cancer.2011;98:1335–1345.
- Doonan JH, Kitsios G. Functional evolution of cyclin dependent kinases.Mol Biotechnol.2009;42:14–29.
- Pines J. Cyclins and cyclin-dependent kinases: Take your partners.Trends Biochem Sci.1993;18:195–197.
- Malumbres M. Therapeutic opportunities to control tumor cell cycles.Clin Transl Oncol.2007;8:399–408.
- Cicenas J, Valius M.The CDK inhibitors in cancer research and therapy. J Cancer Res Clin. Oncol. 2011; 137:1409–1418.
- Fisher RP. Secrets of a double agent: CDK7 in cell-cycle control and transcription. J Cell Sci. 2005; 118: 5171–5180.
- Gullick WJ. Prevalence of aberrant expression of the epidermal growth factor receptors in human cancers. Br Med Bull.1991;47(1):87–98.
- Lapenna S, Giordano A. Review: Cell cycle kinases as therapeutic targets for cancer.Nat Rev Drug Discov. 2009; 8:547-566.
- Sausville EA. Review: Complexities in the development of cyclin-dependent kinase inhibitor drugs.Trends Mol. Med. 2002;8(4):532-537.
- Yardern Y, Ullrich A. Growth factor receptor tyrosine kinases.Annu Rev Biochem.1988;57:443-478.
- Pore DM, Patil PB, Gaikwad DS, Hegade PG, Patil JD, Undale KA. Green access to novel spiropyranopyrazole derivatives.Tetrahedron Lett.2013;54:5876-5878.
- Yu J, Zhou Y, Shen T, Mao W, Chen K, Song Q. Novel and efficient one-pot synthesis of spiro [indoline-3,4'- pyrano [2,3-c]pyrazole] derivatives catalysed by L-proline in aqueous medium.J Chem Research.2013;37:365-368.
- www.vlifesciences.com
- Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. Evaluation of a tetrazolium-based semi automated colorimetrie assay: assessment of radio sensitivity. Cancer Res.1987;47:943-946.
- Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.J Immunol Methods.1983;65:55-63.
- Zhao Y, Abraham MH, Lee J, Hersey A, Luscombe NC, Beck G, Sherborne B, Cooper I. Rate-limited steps of human oral absorption and QSAR studies, Pharm. Res. 2002;19:1446-1457.
- Molinspiration Cheminformatics, Bratislava, Slovak Republic. Available from: http://www.molinspiration.com/ services/properties.html
- Tripathi L, Kumar P, Singh R, Stables J, Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothio amides.Eur J of Med Chem.2012;47:153-166.