New Pyrano[2,3-d:6,5-d']dipyrimidine Derivatives-Synthesis, in vitro Cytotoxicity and Computational Studies

Suresh Maddila; Kovashnee Naicker; Sridevi Gorle; Surjyakant Rana; Kotaiah Yalagala; Surya N Maddila; Moganavelli Singh; Parvesh Singh; Sreekantha B Jonnalagadda

doi:10.2174/1871520616666151123095932

New Pyrano[2,3-d:6,5-d']dipyrimidine Derivatives-Synthesis, in vitro Cytotoxicity and Computational Studies

Anticancer Agents Med Chem. 2016;16(8):1031-1037. doi: 10.2174/1871520616666151123095932.

Authors

Suresh Maddila, Kovashnee Naicker, Sridevi Gorle, Surjyakant Rana, Kotaiah Yalagala, Surya N Maddila, Moganavelli Singh, Parvesh Singh, Sreekantha B Jonnalagadda¹

Affiliation

¹ Department of Chemistry, School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus, Chiltern Hills, Durban-4000, South Africa.

PMID: 26592746
DOI: 10.2174/1871520616666151123095932

Abstract

A new series of pyrano[2,3-d:6,5-d']dipyrimidine derivatives were synthesized and evaluated for their in vitro anticancer activity. The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR, 15N NMR, HR-MS and FT-IR spectral analyses. The cytotoxic activities of these compounds against four human cancer (HeLa, SKBR-3, HepG2, and Caco-2) cell lines were determined. The synthesized compounds showed high selectivity, and four compounds (5e, 5f, 5g and 5i) showed excellent potent cytotoxicity against HeLa, SKBR-3, and HepG2 cancer cell lines. Furthermore, four other compounds (5a, 5c, 5b and 5d) have exhibited significant cytotoxicity activity in the SKBR-3 and HepG2 cell lines respectively, with moderate cytotoxicity seen in the HeLa cell line. Additionally, a molecular docking study was conducted to predict the anti-cancer behavior of the synthesized compounds via inhibition of the allosteric site of Human Kinesin Eg5.

Keywords: HeLa; HepG2; SKBR-3; Synthesis; cytotoxicity activity; pyranes; pyrimidines.