“…(isolate no. CNH-248), was observed to produce a new pentacyclic polyether, arenaric acid ( 1a ), which is related to two known polyether antibiotics, K41-A ( 2 ) − and oxolonomycin ( 3 ), respectively. …”
Arenaric acid (1a), a new pentacyclic polyether related to the antibiotics K-41A and oxolonomycin, was isolated as its sodium salt (1b) from the culture broth of an estuarine bacterial isolate of the genus Streptomyces. The structure of arenaric acid was established by spectroscopic methods involving comprehensive 2D NMR measurements.
“…(isolate no. CNH-248), was observed to produce a new pentacyclic polyether, arenaric acid ( 1a ), which is related to two known polyether antibiotics, K41-A ( 2 ) − and oxolonomycin ( 3 ), respectively. …”
Arenaric acid (1a), a new pentacyclic polyether related to the antibiotics K-41A and oxolonomycin, was isolated as its sodium salt (1b) from the culture broth of an estuarine bacterial isolate of the genus Streptomyces. The structure of arenaric acid was established by spectroscopic methods involving comprehensive 2D NMR measurements.
“…Bioassay-guided fractionation of the ethyl acetate extract led to the isolation of three compounds (1-3), of which 1 (arenaric acid) and 2 (K41 A) were identified as polyether-type polyketides, by comparison of their spectral data with those previously reported (Fig. 1A) [33][34][35][36].…”
Section: Isolation and Structure Elucidation Of Compounds 1-3mentioning
“…The difference in anti-HIV-1 mechanism between the earlier study and ours might be due to the different structures of polyethers. K-41A and K-41Am have a terminal (F) ring [22], which is rare in polyethers and was only previously found in K-41B [22] and CP-96,797 [21]. Thus, this rare terminal (F) ring may play an important role in the anti-HIV-1 activity of K-41A and K-41Am.…”
Section: Discussionmentioning
confidence: 89%
“…K-41A and K-41Am attach a terminal (F) ring [22]. This terminal (F) ring is rare and was only previously found in K-41A, K-41B [22], and CP-96,797 [21]. In this study, we characterised the anti-HIV-1 activity of K-41A and K-41Am as well as the mechanisms involved.…”
Section: Introductionmentioning
confidence: 92%
“…The molecular structures of K-41A and K-41Am are shown in Figure 1. K-41A and K-41Am attach a terminal (F) ring [22]. This terminal (F) ring is rare and was only previously found in K-41A, K-41B [22], and CP-96,797 [21].…”
Introduction: K-41A is a known compound with antibacterial activity against gram-positive bacteria and coccidia. In our screening of anti-HIV compounds, we found polyether antibiotic K-41A and its analogue K-41Am isolated from a marine-derived Streptomyces sp. SCSIO 01680 exhibited anti-HIV activity. Material and methods: In this study, we characterised the anti-HIV activity of K-41A and K-41Am as well as the mechanism(s) involved. The dose-dependent inhibitory effects of K-41A and K-41Am on HIV-1 replication were observed in the TZM-bl-HIV-1 IIIB system, MT-2-HIV-1 IIIB system, and peripheral blood mononuclear cells (PBMCs)-HIV-1 BaL system. The 50% inhibitory concentrations (IC 50) of K-41A on HIV-1 replication in three systems were 0.75 μM, 0.09 μM, and 0.13 μM, respectively, and the selective indexes (SIs) were 5.81, 49.44, and 598.00, respectively. The IC 50 of K-41Am in three systems were 5.57 μM, 0.24 μM, and 1.15 μM, respectively, and the SIs were > 1.04, 80.71, and > 5.03, respectively. Results: Mechanism research demonstrates that two compounds inhibited the activities of HIV-1 reverse transcriptase (RT) and integrase (IN) in a dose-dependent manner. Molecular docking shows that the docking scores were relatively high between the compound and HIV-1 RT or IN. Conclusions: K-41A and K-41Am possess anti-HIV-1 activity via a multi-target inhibition mechanism, which provides a novel molecular pattern for anti-HIV drug design and structural modification to improve the anti-HIV activity.
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