Structure activity relationship of arylidene pyrrolo and pyrido [2,1-b] quinazolones as cytotoxic agents: synthesis, SAR studies, biological evaluation and docking studies

• Published in: Medicinal chemistry (Shp-sariqah, United Arab Emirates) Vol. 9; no. 5; p. 642
• Main Authors: Mangla, Veenu, Nepali, Kunal, Singh, Gagandip, Singh, Jagjeet, Guru, Santosh, Gupta, Manish Kumar, Mahajan, Priya, Saxena, Ajit Kumar, Lal Dhar, Kanaya
• Format: Journal Article
• Language: English
• Published: Netherlands 01-08-2013
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HL-60 Cells; Humans; MCF-7 Cells; Molecular Docking Simulation; Molecular Structure; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyridines - chemical synthesis; Pyridines - chemistry; Pyridines - pharmacology; Quinazolinones - chemical synthesis; Quinazolinones - chemistry; Quinazolinones - pharmacology; Structure-Activity Relationship
• ISSN: 1875-6638
• DOI: 10.2174/1573406411309050003

Tubulin is the one of the most useful and strategic molecular targets for anticancer drugs. Agents that bind in Colchicine-binding site of tubulin include Phenstatin, Combretastatin A-4, Colchicine, Steganacin, Podophyllotoxin and certain other synthetic analogues of these compounds. Arylidene pyrollo and pyrido [2,1- b] quinazolones (isoindigatone and its synthetic analogues) have been earlier reported to be tubulin inhibitors evidenced by tubulin polymerization assay. The present study is an extension of the library of the isoindigatone and its synthetic analogues to generate the structure activity relationship. The study explores the role of the arylidene ring and also provides some intresting observations such as the placement of bicyclic ring such as naphylidene for potential activity. Some of the important interactions of KNH- 3 and KNH-11 with the amino acid residues of active site of Tubulin have also been observed by molecular modeling.