Design and Green Synthesis of Thieno[2,3-d]pyrimidine Analogues as Potential Antiproliferative Agents

Publisher: Bentham Science Publishers

E-ISSN: 1875-5992|17|5|701-711

ISSN: 1871-5206

Source: Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents), Vol.17, Iss.5, 2017-04, pp. : 701-711

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

Background: Despite of significant progress achieved in the chemotherapy of cancer; it is still among theleading cause of morbidity and mortality worldwide.Objective: Taking cognizance of the extensive biological potential of reported thieno[2,3-d]pyrimidines and inspiredby the clinically available anticancer agents dasatinib and gefitinib, 4-substituted thieno[2,3-d]pyrimidines have beensynthesized.Methods: The compounds were synthesized via microwave-assisted methods and screened for their cytotoxic activityagainst liver HepG-2, lung NCI-H522, melanoma A-375, pancreatic MIA PaCa-2 and colon CaCo-2 human cancer celllines using MTT assay.Results: The antiproliferative potential of most active compounds 20b and 20f (piperidino substituted); and 22d(hybrid analogue of Dasatinib) was further assessed and confirmed by calcein AM and colony formation assay, whichrevealed the higher potency of hybrid analogue 22d in comparison to piperidino substituted derivative 20f.Conclusion: Flow cytometer based cell cycle perturbation experiments revealed that antiproliferative effects of themost active compound 22d was associated with increased proportion of cells in the G2/M and subG0/G1 phases of thecell cycle. In silico ADME studies also confer the drug like characteristics of the potent compounds.

Related content