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  3. Synthesis of novel hetero ring fused pyridine derivatives; Their anticancer activity, CoMFA and CoMSIA studies

Synthesis of novel hetero ring fused pyridine derivatives; Their anticancer activity, CoMFA and CoMSIA studies

  • Bioorg Med Chem Lett. 2018 Jul 15;28(13):2328-2337. doi: 10.1016/j.bmcl.2018.04.031.
G Santhosh Kumar 1,  Y Poornachandra 2,  Shravan Kumar Gunda 3,  K Ratnakar Reddy 1,  Jaheer Mohmed 3,  Kamal Shaik 4,  C Ganesh Kumar 2,  B Narsaiah 5
Affiliations

Affiliations

  • 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.
  • 5 Fluoro Organic Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India. Electronic address: narsaiah@iict.res.in.
PMID: 29798826 DOI: 10.1016/j.bmcl.2018.04.031
Abstract

A series of novel furo[2,3-b]pyridine-2-carboxamide 4a-h/pyrido[3',2':4,5]furo[3,2-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 furo[2,3-b]pyridine-2-carbohydrazide Schiff's Bases 7a-h and pyrido [3',2':4,5]furo[3,2-d]pyrimidin-4(3H)-one derivatives 8a-h starting from furo[2,3-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.

Keywords

3D QSAR; Anti-cancer activity; Carbohydrazide Schiff’s bases; CoMFA and CoMSIA studies; Pyrido[3′,2′:4,5]furo[3,2-d]pyrimidin-4(3H)-one.

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