Structure activity relationship of arylidene pyrrolo and pyrido [2,1-b] quinazolones as cytotoxic agents: synthesis, SAR studies, biological evaluation and docking studies.
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.
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab- 143005, India.
Veenu
V
Mangla
Kunal
K
Nepali
Gagandip
G
Singh
Jagjeet
J
Singh
Santosh
S
Guru
Manish Kumar
MK
Gupta
Priya
P
Mahajan
Ajit Kumar
AK
Saxena
Kanaya
K
Lal Dhar
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011720:Pyrazoles; D011725:Pyridines; D052999:Quinazolinones