Design, synthesis, and biological evaluation of 1,8‐naphthyridine glucosamine conjugates as antimicrobial agents

Abstract

In the quest for discovering potent antimicrobial agents with lower toxicity, we envisioned the design and synthesis of nalidixic acid‐D‐(+)‐glucosamine conjugates. The novel compounds were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive bacteria, Gram negative bacteria and fungi. Cytotoxicity using MTT assay over L6 skeletal myoblast cell line, ATCC CRL‐1458 was carried out. In vitro antimicrobial assay revealed that 1‐ethyl‐7‐methyl‐4‐oxo‐N‐(1,3,4,6‐tetra‐O‐acetyl‐2‐deoxy‐D‐glucopyranose‐2‐yl)‐[1,8]‐naphthyridine‐3‐carboxamide (5) and 1‐ethyl‐7‐methyl‐4‐oxo‐N‐(2‐deoxy‐D‐glucopyranose‐2‐yl)‐[1,8]‐naphthyridine‐3‐carboxamide(6) possess growth inhibitory activity against resistant Escherichia coli NCTC, 11954 (MIC 0.1589 mM) and Methicillin resistant Staphylococcus aureus ATCC, 33591 (MIC 0.1589 mM). Compound (5) was more active against Listeria monocytogenes ATCC 19115 (MIC 0.1113 mM) in comparison with the reference nalidixic acid (MIC 1.0765 mM). Interestingly, compound (6) had potential antifungal activity against Candida albicans ATCC 10231 (MIC <0.0099 mM). Remarkably, the tested compounds had low cytotoxic effect. This study indicated that glucosamine moiety inclusion into the chemical structure of the marketed nalidixic acid enhances antimicrobial activity and safety.

Novel 1,8-Naphthyridine Derivatives: Design, Synthesis and in vitro screening of their cytotoxic activity against MCF7 cell line

“…These derivatives play a vital role in therapeutic products [7][8][9]. Naphthyridines derivatives have a wide spectrum of biological effects, for example anti-inflammatory, antimalarial, antifungal, and antibacterial [10][11][12]. Moreover, naphthyridine derivatives displayed good HIV-1 integrase inhibitor profiles and cytotoxicity [13,14].…”

Glucosamine substituted sulfonylureas: IRS–PI3K–PKC–AKT–GLUT4 insulin signalling pathway intriguing agent

“…18,19 These candidates were designed to retain the pharmacophoric features of glimepiride sulfonylurea with the addition of the glucosamine moiety, an analogue to N-acetylglucosamine, one of the cell wall peptidoglycans with clinical and medicinal importance. [19][20][21][22] Contrary to other skeletal muscle cell lines, L6 skeletal muscle cells (a rat cell line) and myotubes (a mouse cell line) have exhibited insulin-dependent glucose uptake in animal muscle cells in culture. 23,24 Hence, they could be adopted to successfully develop an in vitro model to investigate glucose uptake in muscle cells.…”

“…18,19 These candidates were designed to retain the pharmacophoric features of glimepiride sulfonylurea with the addition of the glucosamine moiety, an analogue to N -acetylglucosamine, one of the cell wall peptidoglycans with clinical and medicinal importance. 19–22…”

Design, Synthesis, and Antifungal Activities of Hymexazol Glycosides Based on a Biomimetic Strategy

“…When indomethacin was glycosylated with GlcN, the enzymatic inhibitory activity of the new glycoside increased by dozens of times compared to indomethacin . Moreover, it is known that amino sugars can significantly improve the drug-like properties of active compounds after glycosylation, such as increased water solubility and reduced cytotoxicity. , GlcN and GlcNAc, as rich biological resources, have played a great role in the medical field. However, there are still few studies that address their agricultural applications, and their application value is severely limited.…”