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Bhatia, Manish S.
- Exploration of Anticancer Potential of Spiropyranopyrazole Derivatives as CDK7 Inhibitors
Abstract Views :133 |
PDF Views:26
Authors
Manish S. Bhatia
1,
Santosh S. Kumbhar
1,
Vikram S. Kawade
1,
Prafulla B. Choudhari
1,
Neela M. Bhatia
1,
Sandip B. Patil
2,
Pradip B. Patil
3
Affiliations
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
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.Full Text
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.
- Designing of Colorimetric Reagent and Development of Stability Indicating Method for Analysis of Drugs with Fumarate Salt
Abstract Views :119 |
PDF Views:1
Authors
Swapnil D. Jadhav
1,
Sharad C. Sarak
1,
Tushar S. Nimbalkar
1,
Manish S. Bhatia
1,
Harinath N. More
1
Affiliations
1 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Near Chitranagari, Kolhapur – 416 013, M. S., IN
1 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Near Chitranagari, Kolhapur – 416 013, M. S., IN
Source
Asian Journal of Pharmaceutical Analysis, Vol 4, No 1 (2014), Pagination: 31-35Abstract
The Tenofovir Disoproxil, Ferrous, Bisoprolol and Ketotifen were used in marketed formulations in the form of fumaric acid salt due to stability and solubility purposes. Stability of marketed formulation is an important aspect that needs special attention over the period of time. Designing of colorimetric reagent (3, 5 Dinitro Benzoic Acid) and development of analytical method has been carried out for estimation of fumaric acid from marketed formulations which indirectly quantifies Bisoprolol and Ketotifen. The fumaric acid shows linearity in concentration range of 100- 700 ng/mL. The result of analysis of marketed formulation of Bisoprolol and Ketotifen we found to be within 98.00 to 102 % with RSD value of less than 2 %. The forced degradation studies of Bisoprolol and Ketotifen was carried out which shows degradation less than 20 % and results were accurate and precise. The method was validated using ICH Q2B (R1) guidelines. The method was found to be simple, accurate, precise, sensitive and selective.
- Application of Metanil Yellow for the Extractive Spectrophotometric Determination of Norfluoxetine
Abstract Views :95 |
PDF Views:0
Authors
Affiliations
1 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Near Chitranagri, Kolhapur-416013, IN
1 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Near Chitranagri, Kolhapur-416013, IN