Document Detail

Synthesis of novel 3,5-diaryl pyrazole derivatives using combinatorial chemistry as inhibitors of tyrosinase as well as potent anticancer, anti-inflammatory agents.
MedLine Citation:
PMID:  20638287     Owner:  NLM     Status:  MEDLINE    
In the present article, we have synthesized a combinatorial library of 3,5-diaryl pyrazole derivatives using 8-(2-(hydroxymethyl)-1-methylpyrrolidin-3-yl)-5,7-dimethoxy-2-phenyl-4H-chromen-4-one (1) and hydrazine hydrate in absolute ethyl alcohol under the refluxed conditions. The structures of the compounds were established by IR, (1)H NMR and mass spectral analysis. All the synthesized compounds were evaluated for their anticancer activity against five cell lines (breast cancer cell line, prostate cancer cell line, promyelocytic leukemia cell line, lung cancer cell line, colon cancer cell line) and anti-inflammatory activity against TNF-alpha and IL-6. Out of 15 compounds screened, 2a and 2d exhibited promising anticancer activity (61-73% at 10 microM concentration) against all selected cell lines and IL-6 inhibition (47% and 42% at 10 microM concentration) as in comparison to standard flavopiridol (72-87% inhibition at 0.5 microM) and dexamethasone (85% inhibition at 1 microM concentration), respectively. Cytotoxicity of the compounds checked using CCK-8 cell lines and found to be nontoxic to slightly toxic. Out of 15, four 3,5-diaryl pyrazole derivatives exhibiting potent inhibitory activities against both the monophenolase and diphenolase actions of tyrosinase. The IC(50) values of compounds (2a, 2d, 2h and 2l) for monophenolase inhibition were determined to range between 1.5 and 30 microM. Compounds 2a, 2d, 2h and 2l also inhibited diphenolase significantly with IC(50) values of 29.4, 21.5, 2.84 and 19.6 microM, respectively. All four 3,5-diaryl pyrazole derivatives were active as tyrosinase inhibitors (2a, 2d, 2h and 2l), and belonging to competitive inhibitors. Interestingly, they all manifested simple reversible slow-binding inhibition against diphenolase.
Babasaheb P Bandgar; Jalinder V Totre; Shrikant S Gawande; C N Khobragade; Suchita C Warangkar; Prasad D Kadam
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Publication Detail:
Type:  Journal Article     Date:  2010-06-19
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  18     ISSN:  1464-3391     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-09     Completed Date:  2010-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  6149-55     Citation Subset:  IM    
Copyright Information:
Copyright 2010. Published by Elsevier Ltd.
Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur, India.
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MeSH Terms
Agaricales / enzymology
Anti-Inflammatory Agents / chemical synthesis,  chemistry*,  pharmacology*
Antineoplastic Agents / chemical synthesis,  chemistry*,  pharmacology*
Cell Line, Tumor
Cytokines / immunology
Drug Screening Assays, Antitumor
Models, Molecular
Monophenol Monooxygenase / antagonists & inhibitors*,  metabolism
Neoplasms / drug therapy
Pyrazoles / chemical synthesis,  chemistry*,  pharmacology*
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Antineoplastic Agents; 0/Cytokines; 0/Pyrazoles; 288-13-1/pyrazole; EC Monooxygenase

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