Synthesis, Antimicrobial, and Anticancer Activities of a New Series of Thieno[2,3‐d] Pyrimidine Derivatives

Abstract

A new series from thieno[2,3‐d] pyrimidine derivatives have been synthesized based on 2‐(ethylmercapto)‐4‐mercapto‐6‐phenyl‐5‐pyrimidine carbonitrile, these compounds used in the synthesis of many pyrimidothienopyrimidine derivatives and triazolo[1″,5″:1″,6″]pyrimido[4′,5′:4,5]thieno[2,3‐d] pyrimidine derivatives. The chemical composition of these compounds was confirmed by 1H NMR, 13C NMR, and MS techniques. Some of the synthesized compounds were screened for their antimicrobial and anticancer agent. Compound (9b) showed strong effect on Aspergillus Fumigatus (RCMB 2568), Candida albicans (RCMB 05036), Saphylococcus aureus (RCMB 010010), Bacillis subtilis (RCMB 010067), Salmonella sp. (RCMB 010043), and Escherichia coli (RCMB 010052). Compounds (2) and (5a–k) were evaluated for their IC50 values against two cancer cell lines (MCF‐7 and HeLa cells) in the presence of Paclitaxel as reference material. Compound (5g) showed the highest cytotoxicity against MCF‐7 (IC50 values about 18.87 ± 0.2 μg/mL) cells compared with Paclitaxel (IC50 values about 40.37 ± 1.7 μg/mL). Also, compound (5d) showed the highest cytotoxicity against HeLa (IC50 values about 40.74 ± 1.7 μg/mL) cells compared with Paclitaxel (IC50 values about 45.78 ± 0.8 μg/mL).

Synthesis and Cytotoxicity of Some Thieno[2,3-d]pyrimidine Derivatives

“…Compound 5 was converted into 2‐(ethylmercapto)‐4‐chloro‐6‐phenylpyrimidine‐5‐carbonitrile ( 6) via reaction with POCl 3 . The chlorine underwent nucleophilic displacement with the mercapto group using thiourea in refluxed ethanol to give 2‐(ethylmercapto)‐4‐mercapto‐6‐phenylpyrimidine‐5‐carbonitrile ( 7 ) …”

“…In view of the cytotoxicity of thienopyrimidines, and in continuation of our work on the synthesis of thienopyrimidines, here we report the synthesis of some thienopyrimidines and evaluate their cytotoxicity.…”

Synthesis, reactions, and biological study of some new thienopyrimidine derivatives as antimicrobial and anti‐inflammatory agents

“…Recently, a large number of thienopyrimidines and fused thienopyrimidines were found to possess promising anti‐inflammatory and antimicrobial activities, as shown in Figure . Based on the above‐mentioned facts, and in continuation of our work on biologically active nitrogen and sulfur heterocycles, we report here the synthesis of some new thienopyrimidine derivatives aiming at developing more active antimicrobial and anti‐inflammatory agents.…”

Efficient Synthesis and Biological Evaluation of 2,4‐Diaminothieno[2,3‐d]pyrimidine Derivative

“…In the past few decades, cancer is a leading cause of morbidity and mortality worldwide, so identifying new chemical substances which may act as leads for discovering new potent antitumor agents is critically desirable. The derivatives of fused pyrimidines such as furo[2,3‐d]pyrimidine and thieno[2,3‐d]‐ pyrimidine have been attracted considerable attention as templates for drug discovery for several decades because of their remarkable biological activities including anti‐inflammatory, antiviral, analgesic, antiproliferative, and anti‐ microbial activities, whereas others were used as tyrosine kinase, dnase I inhibitory and Vascular Endothelial Growth Factor Receptor 2 (VEGFR‐2) kinase inhibitors . In addition, thieno[2,3‐d]‐pyrimidines and furo[2,3‐d]pyrimidines as bioisosters of quinazoline derivatives existing in anticancer medicines, such as gefitinib, erlotinib and tandutinib (Figure ).…”