Biological activities of synthetic heterocyclic compounds and natural secondary metabolite produced from Boesenbergia rotunda roots actinomyces.

Abstract

Heterocyclic compounds are often found to be part of the structure of many biologically active substances, including anticancer, antibacterial anti-inflammatory activities. It has also been found to be part of plant growth regulators. At present, heterocyclic compounds have been structurally developed through extensive synthesis in order to obtain better bioactive compounds. Herein, we synthesize heterocyclic derivatives in two synthetic routes. The substituent on the pyrrole and furan rings were selectively modified by substitution, reduction, Wittig and hydrolysis reactions. However, all synthetic routes of heterocyclic derivatives were not successful.

Moreover, Actinomyces crude extract was found many biological activities. Boesenbergia rutunda Actinomyces (Streptomyces, IP-M01) crude extract have an antibacterial, antioxidant and anticancer activities. Researcher was interested in studying the biological activity of purified active compound in this crude extract and further development the structure by chemical synthesis methods. This crude extract didn’t have active purified compound which was identified by bioautography.

Lansai A-D (26-29) are 2,5-DKP derivatives that was isolated from Streptomyces sp. SUC1. The cytotoxicity of lansai A-D (26-29) were low toxicity against Hela and LLC-MK2 cell lines, which lansai C and D (28-29) were displayed an anti-inflammatory effect on RAW 264.7 cells. In this study, we synthesized lansai C and D derivatives by formation of 2,5 DKP ring from dipepetide and modified C-substituent by using one-pot Aldol condensation and substituent at N-position of DKP ring. The lansai C and D (28-29) and its derivatives were evaluated in influenza virus (H5N2) propagation inhibition by using hemagglutination assay. Lansai C (28) and derivatives 63, 65, 74a-74d, 296c were showed negative results. The molecular docking study was found that lansai C (28) and compound 74d can form H-bonds with the amino acids in the active site of the enzymes, HGPRT, H5N2, SARS-CoV-2 3CLpro and SARS-CoV-2 RBD with ACE2, with low binding energy than favipiravir. Lansai C (28), lansai D (29) and its derivatives (63-66, 74a-e, 74g, 296a-c) were evaluated the antibacterial activity which showed low activities against S. aureus and E. coli (MIC > 512 µg/mL).

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