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

Author(s): Rupinder Kaur Gill, Virender Kumar, Mahendra Bishnoi, Kamalendra Yadav, Kanthi Kiran Kondepudi, Jitender Bariwal*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 17 , Issue 5 , 2017

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Graphical Abstract:


Background: Despite of significant progress achieved in the chemotherapy of cancer; it is still among the leading cause of morbidity and mortality worldwide.

Objective: Taking cognizance of the extensive biological potential of reported thieno[2,3-d]pyrimidines and inspired by the clinically available anticancer agents dasatinib and gefitinib, 4-substituted thieno[2,3-d]pyrimidines have been synthesized.

Methods: The compounds were synthesized via microwave-assisted methods and screened for their cytotoxic activity against liver HepG-2, lung NCI-H522, melanoma A-375, pancreatic MIA PaCa-2 and colon CaCo-2 human cancer cell lines 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, which revealed 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 the most active compound 22d was associated with increased proportion of cells in the G2/M and subG0/G1 phases of the cell cycle. In silico ADME studies also confer the drug like characteristics of the potent compounds.

Keywords: Microwave irradiation, thieno[2, 3-d]pyrimidines, antiproliferative, calcein AM assay, colony formation assay, cell cycle analysis.

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Article Details

Year: 2017
Published on: 28 April, 2017
Page: [701 - 711]
Pages: 11
DOI: 10.2174/1871520616666160817142647
Price: $65

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