Design,synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin |
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| Institution: | 1. Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India;2. Gynecologic Oncology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, Maharashtra, India;1. Discipline of Chemistry, Indian Institute of Technology Gandhinagar, Gujarat, India-382355;2. Discipline of Biological Engineering, Indian Institute of Technology Gandhinagar, Gujarat, India-382355 |
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| Abstract: | Three series of novel sulfonylurea podophyllotoxin derivatives were designed, synthesized, and evaluated for in vitro cytotoxicity against four tumor cell lines (A-549, DU-145, KB and KBvin). Compounds 14c (IC50: 1.41–1.76 μM) and 14e (IC50: 1.72–2.01 μM) showed superior cytotoxic activity compared with etoposide (IC50: 2.03 to >20 μM), a clinically available anticancer drug. Significantly, most of the compounds exhibited comparable cytotoxicity against the drug-resistant tumor cell line KBvin, while etoposide lost activity completely. Preliminary structure–activity relationship (SAR) correlations indicated that the 4′-O-methyl functionality in podophyllotoxin analogues may be essential to maintain cytotoxic activity, while an arylsulfonylurea side chain at podophyllotoxin’s 4β position can significantly improve cytotoxic activity. |
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| Keywords: | Podophyllotoxin Sulfonylurea Synthesis Cytotoxic activity |
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