Publication: Synthesis of Isocryptolepine-Triazole Adducts and Evaluation of Their Cytotoxic Activity
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Issued Date
2021-12-14
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ISSN
18607187
18607179
18607179
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2-s2.0-85116997112
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Mahidol University
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SCOPUS
Bibliographic Citation
ChemMedChem. Vol.16, No.24 (2021), 3750-3762
Suggested Citation
Warabhorn Rodphon, Pavitra Laohapaisan, Nantamon Supantanapong, Onrapak Reamtong, Lukana Ngiwsara, Kriengsak Lirdprapamongkol, Charnsak Thongsornkleeb, Nisachon Khunnawutmanotham, Jumreang Tummatorn, Jisnuson Svasti, Somsak Ruchirawat Synthesis of Isocryptolepine-Triazole Adducts and Evaluation of Their Cytotoxic Activity. ChemMedChem. Vol.16, No.24 (2021), 3750-3762. doi:10.1002/cmdc.202100554 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/75885
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Title
Synthesis of Isocryptolepine-Triazole Adducts and Evaluation of Their Cytotoxic Activity
Abstract
Eighteen hybrid compounds between 8-bromo-2-fluoro-isocryptolepine (4) and 1,2,3-triazole were synthesized via azide rearrangement-annulation reaction. Compound 4 underwent regioselective N-propargylation and click reaction to form 8-bromo-2-fluoro-isocryptolepine-triazole hybrids 11 which were evaluated for cytotoxic activity. Compound 11 c containing 1-anisyltriazole was the most effective in inhibiting HepG2, HuCCA-1 and A549 cell lines (IC50 values of 1.65–3.07 μM) while compounds 11 a (1-phenyltriazole), 11 j (1-para-CF3-benzyltriazole) and 11 l (1-meta-Cl-benzyltriazole) were potent inhibitors of HuCCA-1, HepG2 and A549 cell lines, respectively. Moreover, 11 l showed the lowest cytotoxicity to normal human kidney cell line. Compounds 11 c and 11 l provided improvement of cytotoxic activity over 4. Compounds 4, 11 c and 11 l were selected to investigate their mechanisms of action. The results showed that 4 could induce G2/M cell cycle arrest and was involved in the upregulation of p53 and p21 proteins. However, the mechanisms of growth inhibition by 11 c and 11 l were associated with G0/G1 cell cycle arrest and mediated by induction of oxidative stress.