title: Synthesis and antitumor activity of duocarmycin derivatives: modification of segment A of duocarmycin B2.
abstract: Several A-ring pyrrole derivatives of duocarmycin B2 were synthesized effectively from the 3-hydroxy compounds by utilizing an interesting acid-catalyzed rearrangement, their anticellular activity was preliminarily evaluated by assays of growth inhibition of HeLa S3 cells (in vitro) and antitumor activity against murine sarcoma 180 (in vivo). The 8-O-N,N-dialkylcarbamoyl derivatives of the A-ring pyrrole compound showed remarkably potent in vivo antitumor activity, superior to that of duocarmycin B2. these derivatives were subjected to further biological evaluation. They exhibited potent antitumor activity toward murine solid tumors including M5076 sarcoma, B-16 melanoma and Colon 26 adenocarcinoma. Their most noteworthy feature was their efficacy against various human xenografts including LC-6 (lung), St-4 (stomach), and Co-3 (colon).
authors.affiliation: Kyowa Hakko Kogyo Co., Ltd., Tokyo Research Laboratories, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nagamura
authors.forename: A
authors.initials: A
authors.lastname: Asai
authors.forename: Y
authors.initials: Y
authors.lastname: Kanda
authors.forename: E
authors.initials: E
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Gomi
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D000080890:Duocarmycins; D006367:HeLa Cells; D006801:Humans; D007211:Indoles; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011760:Pyrrolidinones / Q000737:chemistry / Q000494:pharmacology; D012510:Sarcoma 180 / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D000903:Antibiotics, Antineoplastic; D000080890:Duocarmycins; D007211:Indoles; D011760:Pyrrolidinones; C060649:duocarmycin B2