title: Design, synthesis and anticancer activity evaluation of some novel pyrrolo[1,2-a]azepine derivatives.
abstract: A novel series of pyrrolo[1,2-a]azepine derivatives 3-7 were synthesized and their structures were confirmed by spectral and elemental analyses. Antitumor activity evaluation of these compounds was carried out against liver (HepG2), breast (MCF7), and colon (HCT116) cancer cell lines using the sulforhodamine-B (SRB) assay method and doxorubicin as reference standard. Compounds 3 and 6 were found to be more potent than doxorubicin against HepG2 cells, with IC50 values of 4, 1.6 and 10.8 nM, respectively. Moreover, compounds 3 and 7 showed broad-spectrum anticancer activity against all the tested cell lines, and their IC50 values were in the nanomolar range (4-44.2 nM and 20.7-45.4 nM, respectively). The 2-benzoylamino derivative of pyrrolo[1,2-a]azepine 5b was the most potent one against MCF7 cells (IC50 of 10.7 nM); however, the 2-(2-chloro-acetylamino)-pyrroloazepine derivative 6 was the most potent against the HCT116 cell line, with an IC50 value of 21.1 nM. The novel compounds were docked into the active site of cyclin-dependent kinase 2 (CDK2) to explore the ability of these compounds to interact with these kinases. All compounds showed a lower binding score energy than the reference ligand.
authors.affiliation: Pharmaceutical Chemistry Department, College of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia; Faculty of Pharmacy, Medicinal Chemistry Department, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Amany
authors.initials: A
authors.lastname: Belal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011485:Protein Binding; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; D011758:Pyrroles; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2
keywords: Antitumor; Pyrimidopyrroloazepine; Pyrrolo[1,2-a]azepine; Pyrroloazepine derivatives