title: Analogs of the marine alkaloid makaluvamines: synthesis, topoisomerase II inhibition, and anticancer activity.
abstract: Twelve analogs of makaluvamines have been synthesized. These compounds were evaluated for their ability to inhibit the enzyme topoisomerase II. Five compounds were shown to inhibit topoisomerase catalytic activity comparable to two known topoisomerase II targeting control drugs, etoposide and m-AMSA. Their cytotoxicity against human colon cancer cell line HCT-116 and human breast cancer cell lines MCF-7 and MDA-MB-468 has been evaluated. Four makaluvamine analogs exhibited better IC(50) values against HCT-116 as compared to control drug etoposide. One analog exhibited better IC(50) value against HCT-116 as compared to m-AMSA. All 12 of the makaluvamine analogs exhibited better IC(50) values against MCF-7 and MDA-MB-468 as compared to etoposide as well as m-AMSA.
authors: Department of Chemistry, University of Alabama at Birmingham, 901 14th Street South, Birmingham, AL 35294, USA.
authors: Bidhan A
authors: BA
authors: Shinkre
authors: Kevin P
authors: KP
authors: Raisch
authors: Liming
authors: L
authors: Fan
authors: Sadanandan E
authors: SE
authors: Velu
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000677:Amsacrine / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008386:Marine Biology; D015394:Molecular Structure; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D011758:Pyrroles; D015363:Quinolones; D059005:Topoisomerase II Inhibitors; C428188:makaluvamine A; D000677:Amsacrine