Cytotoxic Indolocarbazoles fromActinomadura melliauraATCC 39691

Abstract

Actinomadura melliaura ATCC 39691, a strain isolated from a soil sample collected in Bristol Cove, California, is a known producer of the disaccharide-substituted AT2433 indolocarbazoles (6–9). Reinvestigation of this strain using new media conditions led to >40-fold improvement in the production of previously reported AT2433 metabolites and the isolation and structure elucidation of the four new analogues, AT2433-A3, A4, A5, and B3 (1–4). The availability of this broader set of compounds enabled a subsequent small antibacterial/fungal/cancer SAR study that revealed disaccharyl substitution, N-6 methylation, and C-11 chlorination as key modulators of bioactivity. The slightly improved anticancer potency of the newly reported N-6-desmethyl 1 (compared to 6) contrasts extensive SAR of monoglycosylated rebeccamycin-type topoisomerase I inhibitors where N-6 alkylation has contributed to improved potency and ADME. Complete 2D NMR assignments for the known metabolite BMY-41219 (5) and 13C NMR spectroscopic data for the known analogue AT2433-B1 (7) are also provided for the first time.

Structure and specificity of a permissive bacterial C-prenyltransferase

“…Antimicrobial activities were determined following a previously reported protocol 30 . Strain growth also followed our prior protocol 11 where LB medium (BD244620) was used for B. subtilis and Middlebrook 7H9 with OADC enrichment (Sigma-Aldrich) for M. aurum .…”

“…Strain growth also followed our prior protocol 11 where LB medium (BD244620) was used for B. subtilis and Middlebrook 7H9 with OADC enrichment (Sigma-Aldrich) for M. aurum . Cancer cell-line cytotoxicity assays as a measure of general eukaryotic cell toxicity employed the human lung non-small-cell carcinoma cell line A549 as previously reported 30 .…”

Spoxazomicin D and Oxachelin C, Potent Neuroprotective Carboxamides from the Appalachian Coal Fire-Associated Isolate Streptomyces sp. RM-14-6

“…24,30,75 Antibacterial/antifungal MIC values were obtained after 16–48 h of incubation (Table S4). Kanamycin and ampicillin ( S. aureus , M. luteus , S. enterica , and E. coli ), amphotericin B ( S. cerevisiae ), and actinomycin D (non-small-cell lung A549) were used as positive controls (Table S4 and Figure S10).…”

In silico and in vitro research of potential antineoplastic amino acid derivatives of indolocarbazol glycosides properties

“…В настоящее время проходят II-III фазы клинических испытаний разработанные на основе соединений этого класса производные противоопухолевого антибиотика ребеккамицина эдотекарин и бекатекарин, производное алкалоида стауроспорина мидостаурин [6]. Тем не менее продолжается поиск новых противоопухолевых агентов класса индолокарбазолов путем выделения из природных источников методами химического синтеза [7][8][9]. Введение различных заместителей в молекулу индолокарбазола, в первую очередь к атомам азота индола и / или имидного атома азота 5-членного цикла, позволяет модулировать физико-химические и биологические свойства полученных соединений [10].…”