Synthesis and Evaluation of Cytotoxic Activity of Certain Benzo[h]chromene Derivatives

Abstract

Background: Benzo[h]chromenes attracted great attention because of their widespread biological activities, including anti-proliferate activity, and the discovery of novel effective anti-cancer agents is imperative.

Objective: The main objective was to synthesize new benzo[h]chromene derivatives and some reported derivatives, and then test all of them for their anti-cancer activities.

Methods: The structures of the newly synthesized derivatives were confirmed by elemental and spectral analysis (IR, Mass, ¹H-NMR and ¹³C-NMR). 35 compounds were selected by the National Cancer Institute (NCI) for single-dose testing against 60 cell lines and 3 active compounds were selected for 5-doses testing. Also, these 3 compounds were tested as EGFR-inhibitors; using sorafenib as standard, and as Tubulin polymerization inhibitors using colchicines as a standard drug. Moreover, molecular docking study for the most active derivative on these 2 enzymes was also carried out.

Results: Compounds 1a, 1c and 2b have the highest activities among all 35 tested compounds especially compound 1c.

Conclusion: compound 1c has promising anti-cancer activities compared to the used standards and may need further modification and investigations.

Keywords: 5-doses testing; Benzo[h]chromene; EGFR-inhibitors; anti-cancer activity; synthesis; tubulin polymerization inhibitors.