Synthesis of novel hetero ring fused pyridine derivatives; Their anticancer activity,CoMFA and CoMSIA studies |
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Authors: | G Santhosh Kumar Y Poornachandra Shravan Kumar Gunda K Ratnakar Reddy Jaheer Mohmed Kamal Shaik C Ganesh Kumar B Narsaiah |
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Institution: | 1. Fluoro Organic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India;2. Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India;3. Bioinformatics Division, PGRRCDE, Osmania University, Hyderabad 500007, India;4. Department of Chemical Engineering, Visvesvaraya National Institute of Technology, Nagpur 440010, India |
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Abstract: | A series of novel furo2,3-b]pyridine-2-carboxamide 4a–h/pyrido3′,2′:4,5]furo3,2-d] pyrimidin-4(3H)-one derivatives 5a–p were prepared from pyridin 2(1H) one 1 via selective O-alkylation with α-bromoethylester followed by cyclization, then reaction with different aliphatic primary amines to obtain 4 and further reaction with triethyl orthoacetate/triethyl orthoformate. Also prepared novel furo2,3-b]pyridine-2-carbohydrazide Schiff’s bases 7a–h and pyrido 3′,2′:4,5]furo3,2-d]pyrimidin-4(3H)-one derivatives 8a–h starting from furo2,3-b]pyridine carboxylate derivatives 3 by reaction with hydrazine hydrate to form 6 and reaction with diverse substituted aldehydes and cyclization. Products 4a–h, 5a–p, 7a–h and 8a–h were screened against four human cancer cell lines (HeLa, COLO205, Hep G2 and MCF 7) and one normal cell line (HEK 293). Compounds 4e, 4f, 4g, 5h, 7c, 7d, 7e and 7f showed significant anticancer activity against all the cell lines at micro molar concentration and found to be non-toxic to normal cell line. Studies for HeLa, COLO205 and MCF-7 using CoMFA and CoMSIA. Models from 3D-QSAR provided a strong basis for future rational design of more active and selective HeLa, COLO205 and MCF-7 cell line inhibitors. |
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Keywords: | Carbohydrazide Schiff’s bases Anti-cancer activity 3D QSAR CoMFA and CoMSIA studies |
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