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  • Bioorganic Chemistry br cells Consequently it could


     Bioorganic Chemistry 88 (2019) 102967
    cells. Consequently, it could be stated that lipophilicity is also one of the determining factors in the cytotoxic potential of this class of com-pounds.
    3.4. Cell cycle analysis
    The cytotoxic intermediate (3), the most effective analog (6f), and one of the moderately cytotoxic compounds (6h) were selected to be investigated in terms of their influence on the cell cycle progression in order to attain insight on the mode of action of these compounds on cancer cells. The distribution of treated and control cells in different phases of cell cycle is presented in Table 3 and Fig. 2. The findings are in line with previous studies which revealed that naphthoquinone based compounds can potentially arrest the G0/G1 phase in MCF-7 cell line [31,41]. By comparison of cell cycle analysis results of cells treated with compounds 3, 6f and 6h with untreated control cells, it could be de-duced that these compounds (specially 3 and 6h), increased the per-centage of cells in G0/G1 phase, while they decreased cells present in the G2/M phase at 10 and 20 μM concentrations.
    3.5. In silico ADMET prediction
    To better understand molecular properties of the potent compounds physicochemical parameters were calculated. As seen in Table 4 Com-pounds 6f and 6h exhibited desirable molecular properties.
    Some ADMET descriptors of mentioned compounds were also pre-dicted in comparison with Doxorubicin as a reference drug (Table 5). According to the results, Caco2 permeability and interstitial Doxorubicin has been calculated to be more than 90%. While BBB and CNS per-meability revealed that the studied compounds are CNS inactive. In addition, compounds were predicted to be either substrate or inhibitors of CYP. Considering these observation compounds 6f and 6 h might be regarded as lead compounds for further studies.
    4. Conclusion
    Novel 1,4-naphthoquinone-1,2,3-triazole hybrids were synthesized and evaluated for their anticancer activity against three human cancer cell lines (MCF-7, HT-29 and MOLT-4). Most of the conjugates dis-played good levels of in vitro cytotoxicity. Compound 6f was the most potent cytotoxic agent against the three tested cell lines and arrested the cell cycle at G0/G1 phase at 10 and 20 μM concentrations. Thus, these preliminary findings can be beneficial for further development of novel improved naphthoquinone-triazole based anticancer agents.
    The authors wish to thank the support of the Vice-Chancellor for Research, Shiraz University of Medical Sciences (Grant No.94-01-12-10743). This study was part of the Pharm.D thesis of Maryam Gholampour.
    Conflict of interest
    The authors confirm that they have no conflict of interest.
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