Usnic Acid Enaminone-Coupled 1,2,3-Triazoles as Antibacterial and Antitubercular Agents.

(+)-Usnic acid, a product of secondary metabolism in lichens, has displayed a broad range of biological properties such as antitumor, antimicrobial, antiviral, anti-inflammatory, and insecticidal activities. Interested by these pharmacological activities and to tap into its potential, we herein present the synthesis and biological evaluation of new usnic acid enaminone-conjugated 1,2,3-triazoles 10-44 as antimycobacterial agents. (+)-Usnic acid was condensed with propargyl amine to give usnic acid enaminone 8 with a terminal ethynyl moiety. It was further reacted with various azides A1-A35 under copper catalysis to give triazoles 10-44 in good yields. Among the synthesized compounds, saccharin derivative 36 proved to be the most active analogue, inhibiting Mycobacterium tuberculosis (Mtb) at an MIC value of 2.5 µM. Analogues 16 and 27, with 3,4-difluorophenacyl and 2-acylnaphthalene units, respectively, inhibited Mtb at MIC values of 5.4 and 5.3 µM, respectively. Among the tested Gram-positive and Gram-negative bacteria, the new derivatives were active on Bacillus subtilis, with compounds 18 [3-(trifluoromethyl)phenacyl] and 29 (N-acylmorpholinyl) showing inhibitory concentrations of 41 and 90.7 µM, respectively, while they were inactive on the other tested bacterial strains. Overall, the study presented here is useful for converting natural (+)-usnic acid into antitubercular and antibacterial agents via incorporation of enaminone and 1,2,3-triazole functionalities.

Bioorganic synthesis, characterization and evaluation of a natural phenolic lipid.

The first synthesis of a phenolic natural monoacylglycerol (1- [11-(ferulyloxy) undecanoyl)] glycerol) was carried out by bioorganic synthesis starting from ferulic acid. The synthetic route of the target lipidic compound was designed involving a chemo-enzymatic approach using immobilized Candida antarctica lipase as biocatalyst in two of the steps conducted in organic medium. The prepared lipidic compound was characterized by using spectral data and evaluated for antimicrobial, antioxidant and cytotoxic studies to examine its potential. The synthesized compound showed moderate antimicrobial activity and showed very good antioxidant activity in DPPH radical scavenging assay and also in oxidation inhibition in soybean oil by differential scanning calorimetry. The cytotoxic studies of the synthetic lipid showed promising activity against A549 and HeLa cancer cell lines with IC50 values of 9.102 and 9.886 µM respectively. The prepared compound can be useful in designing novel phenolic lipids with potential applications in cosmetic and biomedical fields.

Synthesis and biological evaluation of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thioglycosides.

In the present study, the synthesis of 1, 3, 4-thiadiazole-based thioglycosides were accomplished in good yields with employing a convergent synthetic route. The starting material 5-amino-1, 3, 4-thiadiazole-2-thiol and followed by a series of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thiols (4a-4j) were synthesized with different fatty acid chlorides. The glycosylation of compounds 4a-4j were achieved with trichloroacetimidate methodology. Antimicrobial and cytotoxicity activities of title compounds were evaluated. Among the entire compounds lauric acid and myristic acid derivatives showed good and moderate antimicrobial activity. In case of cytotoxicity results of compounds 8a-8j and 9a-9j, the acetate protected short chain (C6:0, C8:0, C10:0) compounds and the free hydroxyl long chain saturated (C16:0, C18:0) and unsaturated (C18:1, C22:1) compounds exhibited good activity against different cancer cell lines. Further, the free hydroxyl compounds 9a, 9c-9j did not show any toxicity towards normal CHO-K1 cell line whereas acylated compounds 8a-8j exhibited toxicity.