title: Fluorescein hydrazones: A series of novel non-intercalative topoisomerase IIα catalytic inhibitors induce G1 arrest and apoptosis in breast and colon cancer cells.
abstract: Fluorescein hydrazones (5 and 7) were synthesized in three/four steps with 82-92% yields. All synthesized compounds were evaluated by topoisomerase I (topo I) and topoisomerase IIα (topo IIα)-mediated relaxation and cell viability assays. Among them, most of the compounds showed topo I & IIα inhibitory activity and nineteen compounds showed strong anti-proliferative activity against various cell lines. In brief, 5e inhibited 53% topo IIα (etoposide 29%) at 20 μM and showed excellent antiproliferative activity against DU145 (1.43 ± 0.04 μM), HCT15 (2.4 ± 0.03 μM) and MCF7 (11.4 ± 0.5 μM) cell lines in comparison with adriamycin, etoposide, and camptothecin. Compounds 5e, 5g and 5h were further evaluated to determine their mode of action. Compounds 5e, 5g and 5h functioned as non-intercalative topo IIα catalytic inhibitor with induction of G1 arrest and activation of apoptotic proteins in dose-dependent manner.
authors.affiliation: Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Mohammad Shahidul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Seojeong
authors.initials: S
authors.lastname: Park
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Chanju
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Adnan A
authors.initials: AA
authors.lastname: Kadi
authors.affiliation: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea. Electronic address: ykwon@ewha.ac.kr.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Kwon
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: afmrahman@ksu.edu.sa.
authors.forename: A F M Motiur
authors.initials: AF
authors.lastname: Rahman
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000187:drug effects*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004264:DNA Topoisomerases, Type I / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019793:Fluorescein; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D006835:Hydrazones; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D019793:Fluorescein
keywords: Apoptosis; Fluorescein; Fluorescein hydrazones; Topoisomerase IIα catalytic inhibitor