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Distinguished Researches in Basic Sciences


Anticancer activity, dual prooxidant/antioxidant effect and apoptosisinduction profile of new bichalcophene-5-carboxamidines


A series of thirteen new aryl/hetarylbichalcophene-5-carboxamidines was prepared and screened for anin vitroanti-proliferative activity against sixty cancer cell lines. The tested monocationic bichalcophenesdisplayed promising potent anticancer activity against most cancer cell lines with GI50values of 1.34e3.09mM. The most potent compound was derivative8(median GI50and TGI values of 1.34 and 3.23mM,respectively)

being also the least cytotoxic in this bichalcophene series with an LC50of 77.6mM. The mostresponsive cancer cell lines were leukemia (SR and K-562) and colon (HCT-15 and HT29) with GI50in thesub-micromolar range. The effect of the tested bichalcophenes on normal human lungfibroblast (WI-38)cell line showed that they exerted their antiproliferative activity outside the realms of causing anytoxicity in normal cells. To study apoptotic profiles of representatives of this class, compounds4h,4i, and8were found to cause significant reductions in cdk1 expression in HCT-116 colon cells by 46, 79, and 84%,respectively versus 52% reduction by 5- Flourouracil (5-FU). These three compounds were also uniquebeing the only derivatives that significantly elevated the expression of p53 by ~2, 4, and 5 folds,respectively. The tested bichalcophenes exhibited moderate to potent antioxidant activity in DPPH andABTS as well as hydroxyl radical scavenging assays. Moreover, compoundsIIIb,IIIc,4c, and4i, showedthe highest pro-oxidant activity. Finally, to aid future endeavors for optimization of this series, a 5descriptor 2D-QSAR model was derived from the common physicochemical parameters of thesebichalcophenes and the external validation proved the model's good predictive efficiency Read more


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