title: Design, synthesis and evaluation of thiohydantoin derivatives as potent topoisomerase I (Top1) inhibitors with anticancer activity.
abstract: DNA topoisomerase I is a potential chemotherapeutic target. Here, we designed and synthesized a library comprising of hydantoin and thiohydantoin derivatives and tested them against human and Leishmania Top1. One of the thiohydantoin compounds with substituted thiophenyl as the central moiety (compound 15) exhibited potent inhibition of human Top1 (HTop1) through stabilization of Top1-DNA cleavage complexes and showed selective anticancer activity against human cervical carcinoma (HeLa) and breast carcinoma (MCF-7) cell lines. Molecular modeling studies with HTop1 rationalized the inhibitory mechanism of compound 15.
authors: Laboratory of Molecular Biology, Department of Physical Chemistry, Indian Association for the Cultivation of Science, 2A and 2B Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India.
authors: Papiya
authors: P
authors: Majumdar
authors: Department of Chemistry, Shiv Nadar University, Post Office Shiv Nadar University, Gautam Buddha Nagar, 201314, Uttar Pradesh, India.
authors: Chandramohan
authors: C
authors: Bathula
authors: Laboratory of Molecular Biology, Department of Physical Chemistry, Indian Association for the Cultivation of Science, 2A and 2B Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India.
authors: Suparna M
authors: SM
authors: Basu
authors: Laboratory of Molecular Biology, Department of Physical Chemistry, Indian Association for the Cultivation of Science, 2A and 2B Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India.
authors: Subhendu K
authors: SK
authors: Das
authors: Department of Life Science, Shiv Nadar University, Post Office Shiv Nadar University, Gautam Buddha Nagar, 201314, Uttar Pradesh, India.
authors: Rahul
authors: R
authors: Agarwal
authors: Department of Chemistry, Shiv Nadar University, Post Office Shiv Nadar University, Gautam Buddha Nagar, 201314, Uttar Pradesh, India.
authors: Santanu
authors: S
authors: Hati
authors: Department of Life Science, Shiv Nadar University, Post Office Shiv Nadar University, Gautam Buddha Nagar, 201314, Uttar Pradesh, India.
authors: Ashutosh
authors: A
authors: Singh
authors: Department of Chemistry, Shiv Nadar University, Post Office Shiv Nadar University, Gautam Buddha Nagar, 201314, Uttar Pradesh, India. Electronic address: subhabrata.sen@snu.edu.in.
authors: Subhabrata
authors: S
authors: Sen
authors: Laboratory of Molecular Biology, Department of Physical Chemistry, Indian Association for the Cultivation of Science, 2A and 2B Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India. Electronic address: pcbbd@iacs.res.in.
authors: Benu Brata
authors: BB
authors: Das
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013867:Thiohydantoins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013867:Thiohydantoins; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I
keywords: Camptothecin; Hydantoin; Leishmania bi-subunit topoisomerase I; Methylfuro[3,4-c]pyridine-3,4(1H,5H)-dione; Thiohydantoin; Topoisomerase I