Acta Pharm. 67 (2017) 275-292


full paper

Original research paper


Synthesis of thiophene and N-substituted thieno[3,2-d]pyrimidine derivatives as potent antitumor and antibacterial agents


1 Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Faculty of Science, Department of Chemistry, P.O.Box 90950 Riyadh 11623, Kingdom of Saudi Arabia

2 Photochemistry Department (Heterocyclic & Nucleosides Unit), National Research Centre, Dokki 12622, Giza, Egypt

3 Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Faculty of Science, Biology Department (Microbiology Unit), P.O.Box 90950 Riyadh 11623, Kingdom of Saudi Arabia

Accepted May 15, 2017

Published online June 14, 2017


A novel series of carbamothioylamino-benzene-sulfonamide-thiophene-carboxylates 4a-c and thieno [3,2-d] pyrimidin-2-yl-amino-benzene-sulfonamides 5a-c were synthesized in a series of synthetic steps and were used as key intermediates for the synthesis of thienotriazolopyrimidine-benzene-sulfonamide derivatives 6a-c and 7a-c. Thieno[3,2-d]pyrimidin-ones (8 and 9) were also prepared. Compound 9 was used as an intermediate for the synthesis of imidazole/1,2,4-triazole and tetrazine functionalized thieno[3,2-d]pyrimidine derivatives (10–12). Pyrrole derivatives/pyrrolopyrimidine/pyrrolo-triazolopyrimidine functionalized thiophenes (15–19) were also synthesized. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. Most of the newly synthesized compounds were evaluated for their in vitro activity against three human tumor cell lines, namely, liver cancer (HepG-2), colon cancer (HT-29) and lung cancer (NCI-H460), using doxorubicin as standard. Compounds 16 (GI50 = 0.02, 0.04 and 0.06 µmol L–1, resp.) and 19b (GI50 = 0.02, 0.03 and 0.05 µmol L–1, resp.) showed higher activity against all cell lines than doxorubicin. Most of the compounds were also screened for antibacterial activity using ciprofloxacin as standard drug. Compounds 4b and 6b, both containing benzenesulfonamide linked to N-, 10 bearing imidazole moiety, and 15 and 19b,c with a thiophene-2-carboxylic acid chain, exhibited high activity against Gram-positive and Gram-negative bacteria.


Keywords: thieno[3,2-d]pyrimidines, thieno[3,2-d][1,2,4]triazolo [1,5-a]pyrimidines, anticancer, antibacterial