Background: Globally, cancer is regarded as one of the biggest health concern in humans and animals and
is one of the most terrifying diseases. Therefore, there is a necessity for the discovery, development and improvement
of novel antitumor drug molecules which could efficiently prevent proliferative pathways and clonal expansion of
cells. Heterocyclic compounds like benzochromene play a key role in the development of current pharmaceuticals,
natural resources, agriculture products, analytical reagents and dyes. Therefore, anticancer drugs show increased
resistance, it is essential to designing the novel structured heterocyclic moieties to create potential anticancer agents
with promising biological applications.
Objective: To synthesis a novel 1-(substitutedphenyl)-2-(1H-tetrazol-5-yl)-1H-benzo[f]chromene-3-amine derivatives
for in vitro antitumour activity.
Method: The reaction of 3-amino-1-(substitutedphenyl)-1H-benzo[f]chromene-2-carbonitrile with sodium azide,
ammonium chloride in dimethyl formamide solvent under reflux condition for 4 h afforded products (3a-k). The
synthesized molecules were subjected to possible potential anti-tumour activity in vitro in four human cancer cell lines
(MCF-7, Caco-2, HeLa and SKBR-3), and one human non-cancer cell line (HEK293), using the MTT cell viability assay.
Results: A novel series of products (3a-k) were synthesized with good yield and were identified with 1
H NMR, 15
C NMR, FT-IR and HR-MS spectrum. The most potent compounds 3d, 3e, and 3f possessing the greatest
cytotoxicity activity with IC50
values slightly higher (15-33 μM) than that of 5-Fluorouracil (10-17 μM), indicating
their potential to be antitumor agents. The 3a, 3b, 3c, 3h, 3i and 3j compounds showed moderate activity.
Additionally, a molecular docking analysis was conducted to predict the multi-drug resistance modulator behavior of
synthesized compounds in the ATP binding site of P-glycoprotein.
Conclusions: We synthesized and designated eleven novel derivatives of tetrazole linked benzochromenes (3a-k) and
evaluated their anti-cancer activity. Additionally, the results from the docking studies were found to be in good
agreement with the results from computational profiling.