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

Author(s):

Samir M. Awad, Mosaad S. Mohamed, Marwa Abd El-Fattah Khodair and Rania H. Abd El-Hameed*   Pages 963 - 986 ( 24 )

Abstract:

<P>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. </P><P> 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. </P><P> 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. </P><P> Results: Compounds 1a, 1c and 2b have the highest activities among all 35 tested compounds especially compound 1c. </P><P> Conclusion: compound 1c has promising anti-cancer activities compared to the used standards and may need further modification and investigations.</P>

Keywords:

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

Affiliation:

Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan, Cairo, Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan, Cairo, Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan, Cairo, Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Helwan, Cairo

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