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Journal of Chemistry
Volume 2016, Article ID 2135893, 12 pages
Research Article

Synthesis of Some Polysubstituted Nicotinonitriles and Derived Pyrido[2,3-d]pyrimidines as In Vitro Cytotoxic and Antimicrobial Candidates

1Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
2Department of Chemistry, Faculty of Science, University of Alexandria, Alexandria, Egypt
3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia
4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt

Received 8 February 2016; Revised 20 April 2016; Accepted 21 April 2016

Academic Editor: Artur M. S. Silva

Copyright © 2016 Hassan M. Faidallah et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The synthesis of polysubstituted pyridines, in addition to some derived pyrido[2,3-d]pyrimidine ring systems supported with chemotherapeutically active functionalities, is described. They were evaluated for their in vitro cytotoxic effects against three different human tumor cell lines (human colon carcinoma HT29, hepatocellular carcinoma Hep-G2, and Caucasian breast adenocarcinoma MCF7). Nine compounds displayed variable cytotoxic potential, among which alkylthio analogs 33, 34, and 37 emerged as the most active members, being almost twice as active as doxorubicin against the colon carcinoma HT29 cell line. In addition, the same three analogs showed a clear differential cytotoxic profile as they exhibited a marginal inhibitory effect on the growth of the normal nontransformed human foreskin fibroblast Hs27 cell line. Meanwhile, nineteen compounds were able to exhibit significant antibacterial activity against both Gram-positive and Gram-negative bacteria, together with moderate antifungal activities. The pyrido[2,3-d]pyrimidine-2(1H)-thione 30 together with its alkylthio derivatives 33 and 34 stemmed as the most active antimicrobial members being equipotent to ampicillin against S. aureus, E. coli, and P. aeruginosa, together with a noticeable antifungal activity against C. albicans. Compounds 33 and 34 could be considered as a promising template for possible dual antimicrobial-anticancer candidates.