New thiophene (2-13) and thienopyrimidine (15-27) derivatives have been synthesized. Twenty three compounds were screened against five cell lines namely; hepatocellular carcinoma (liver) HepG-2, epidermoid carcinoma (larynx) Hep-2, mammary gland (breast) MCF-7, human prostate cancer PC-3 and epithelioid cervix carcinoma HeLa. The results revealed that compounds 15,16,17,24 and 25 showed the highest antitumor activity against all tested cell lines compared to Doxorubicin. In order to explain the expected mode of action of the observed anticancer activity, compounds 15,16,17,24 and 25 were selected to screen their DNA binding affinity and enzyme inhibitory activity against DNA polymerase, thymidylate synthase and tyrosine kinase. The results revealed that the tested compounds showed good DNA binding affinity as well as good inhibitory activity against the three enzymes which might explain the observed anticancer activity of the target compounds.
Bioorganic chemistry. 2018 Sep 13 [Epub ahead of print]
Mahasen M Fouad, Eman R El-Bendary, Ghada M Suddek, Ihsan A Shehata, Mohamed M El-Kerdawy
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: ., Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Horus University, Egypt., Department of Pharmacology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt., Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.