Gwanakosides A and B, 6-Deoxy-α-l-talopyranose-Bearing Aromatic Metabolites from a Streptomyces sp. and Coculture with Pandoraea sp.

Abstract

Single-strain cultivation of a mountain soil-derived Streptomyces sp. GA02 and its coculture with Pandoraea sp. GA02N produced two aromatic products, gwanakosides A and B (1 and 2, respectively). Their spectroscopic analysis revealed that 1 is a new dichlorinated naphthalene glycoside and 2 is a pentacyclic aromatic glycoside. The assignment of the two chlorine atoms in 1 was confirmed by the analysis of its band-selective CLIP-HSQMBC spectrum. The sugars in the gwanakosides were identified as 6-deoxyα-L-talopyranose based on 1 H− 1 H coupling constants, Rotating frame Overhauser enhancement spectroscopy (ROESY) NMR correlations, and chemical derivatization followed by spectroscopic and chromatographic analyses. The absolute configuration of 2, whose production was enhanced approximately 100fold in coculture, was proposed based on a quantum mechanics-based chemical shift analysis method, DP4 calculations, and the chemically determined configuration of 6-deoxy-α-L-talopyranose. Gwanakoside A displayed inhibitory activity against pathogenic bacteria, including Staphylococcus aureus (MIC = 8 μg/mL) and Mycobacterium tuberculosis (MIC 50 = 15 μg/mL), and antiproliferative activity against several human cancer cell lines (IC 50 = 5.6−19.4 μM).

A Survey of Recently Discovered Naturally Occurring Organohalogen Compounds

“…GAO2N generates the dichloro gwanakoside A ( 390 ) and a nonchlorinated analogue. The former is active against five bacterial strains (MIC 8–32 μg/mL), and five cancer cell lines (IC 50 5.6–19.4 μM), but has no antifungal effect …”

Propionylpromazine: Unveiling a Novel Inhibitory Agent AgainstMycobacterium tuberculosis

“…This underscores the urgent need for the development of new drugs and treatment regimens that are shorter and simpler, to improve TB management. Recently, several new chemical entities and antimicrobial compounds have shown promise against the highly drug-resistant M. tuberculosis , including ganfeborole, DprE1 inhibitors, Q203, MmpL3 inhibitors, gwanakosides A, retinestatin, etc (Piton et al, n.d.; Li et al, 2016; Huynh et al, 2022, 2023; Nguyen et al, 2022).…”

Expeditious Synthesis of Gwanakoside A and the Chloronaphthol Glycoside Congeners

“…GA02 by Oh and co-workers in 2022 (Figure ). The unique bis-6-deoxy-α- l -talopyranoside and 2,4-dichloronaphthalene-1,7-diol fragments in 1 have never been previously encountered in secondary metabolites. Interestingly, a structurally analogous compound, patientoside B ( 2 ), isolated from plant roots, shares a dichlorophenol moiety .…”

“…In fact, there are more than 250 Food and Drug Administration-approved drugs containing chlorine . Gwanakoside A ( 1 ) was shown to have significant growth-inhibitory activity against pathogenic bacteria (MIC = 8–32 μg/mL) and weak antiproliferative activity against several human cancer cell lines (IC 50 = 5.6–19.4 μM) . Acknowledging the distinct structural features and biological activities of 1 , we embarked on the synthesis of chloronaphthols and their glycosides, aiming to clarify the intricate relationship between its structure and its activity.…”

“…7 Gwanakoside A (1) was shown to have significant growth-inhibitory activity against pathogenic bacteria (MIC = 8−32 μg/mL) and weak antiproliferative activity against several human cancer cell lines (IC 50 = 5.6−19.4 μM). 5 Acknowledging the distinct structural features and biological activities of 1, we embarked on the synthesis of chloronaphthols and their glycosides, aiming to clarify the intricate relationship between its structure and its activity. Herein, we present an efficient approach to the synthesis of gwanakoside A (1) and 14 of its derivatives and preliminary data on their antibacterial and antitumor activities.…”