Pyramidamycins A-D and 3-hydroxyquinoline-2-carboxamide; cytotoxic benzamides from Streptomyces sp. DGC1

Abstract

Four new benzamides, pyramidamycins A-D (2–5) along with the new natural 3-hydroxyquinoline-2-carboxamide (6) were isolated from the crude extract of Streptomyces sp. DGC1. Additionally, five other known compounds namely 2-aminobenzamide (anthranilamide) (1), 4′,7-dihydroxyisoflavanone (7), 2′-deoxy-thymidine, 2′-deoxy-uridine and adenosine were also isolated and identified. The structures of the new compounds 2–6 were elucidated by 1D and 2D NMR studies along with HRMS analyses. The isolated compounds 1–6 contained the same amide side chain. The isolated compounds 1–7 were biologically evaluated in comparison with landomycin A against a prostate cancer cell line (PC3) and non small cell lung cancer cell line (H460) for 48 hrs and against several bacterialstrains. Pyramidamycin C (4) was the most active compound against both PC3 and H460 cell lines (GI50 = 2.473 μM and GI50 = 7.339 μM, respectively). Benzamides (1–3) demonstrated inhibitory activity against Kocuria rosea B-1106 (a diameter halo of 13±2 mm for 1; 10±2 mm for 2 and 3). Compound 6 was slightly active against both Escherichia coli DH5α and Micrococcus luteus NRRL B-2618 (diameter halos 8±2 mm and 9±2 mm, respectively). Taxonomically, the amplified 500 bp 16S rRNA fragment of the Streptomyces sp. DGC1 had 99% identity (BLAST search) to the 16S rRNA gene of Streptomyces atrovirens strain NRRL B-16357.

Synthesis of 2-anilinobenzimidates, anthranilamides, and 2,3-dihydroquinazolin-4(1H)-ones from N-heterocyclic carbenes of indazole

“…It is well known that the parent compound of II occurs in nature, and an additional source was found recently, as II (R = R´= R´´ = H) was isolated from Streptomyces sp. 6 Concerning the biological activities, derivatives of II have been described recently as substrates for the antibacterial target undecaprenyl pyrophosphate synthase, 7 as modulators of the expression of micro RNAs in neuroblastoma cells which cause cell cycle arrest and apoptosis, 8 as inhibitors for Pseudomonas aeruginosa infections 9 and of SIRT, 10 and of neuronal ion channels. 11 Syntheses and structureactivity relationships of orally active anthranilamide-based factor Xa inhibitors have been studied as well.…”

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

“…2–4,7,8,10,13–17,29,52–70 Likewise, including the new bacterial carboxamides 6 and 7 reported herein, over 60 benzamide derivatives have been reported from bacteria, many of which also reportedly display interesting biological and pharmaceutical properties. 71 Importantly, the current study is the first to assess spoxazomicins or oxachelins in the context of neuroprotection against EtOH-induced damage, where corresponding bioactivity comparisons among the analogues tested highlight the importance of the spoxazomicin D ( 2 ) carboxamide and oxachelin C ( 5 ) salicylate as critical to this newly discovered function. While the molecular mechanism and/or specific target of spoxazomicin D ( 2 ) and oxachelin C within this context remains to be determined, it is important to note that structurally related thiazoline-based pulicatins were recently identified as modulators of Ca 2+ influx in a mouse dorsal root ganglion neuronal assay and as high-affinity ligands for the human serotonin 5-HT 2B receptor.…”

Microbial Natural Products in Drug Discovery

“…They have been considered to be a rich source of unique bioactive compounds since the discovery of penicillin ( Figure 1) in 1929 [34], which was structurally elucidated in 1945 and introduced as the first antibiotic by Fleming, Chain, and Florey [35]. Today, many microbial-originated antibiotics are available in the market, and more than 120 of the most important medicines in use are obtained from terrestrial microorganisms [36]. A large number of bioactive metabolites are used in medicine, agriculture, and industry, but about 100 of them are used for therapeutic purposes, herbicidal activity, growth-promoting agents, or tools for biochemistry [37].…”