Tags

Type your tag names separated by a space and hit enter

Design, synthesis, and biological evaluation of 1,8-naphthyridine glucosamine conjugates as antimicrobial agents.
Drug Dev Res. 2019 02; 80(1):179-186.DD

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.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, Jordan.Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, Jordan.Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, Jordan.Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30570767

Citation

Mohammed, Aya A M., et al. "Design, Synthesis, and Biological Evaluation of 1,8-naphthyridine Glucosamine Conjugates as Antimicrobial Agents." Drug Development Research, vol. 80, no. 1, 2019, pp. 179-186.
Mohammed AAM, Suaifan GARY, Shehadeh MB, et al. Design, synthesis, and biological evaluation of 1,8-naphthyridine glucosamine conjugates as antimicrobial agents. Drug Dev Res. 2019;80(1):179-186.
Mohammed, A. A. M., Suaifan, G. A. R. Y., Shehadeh, M. B., & Okechukwu, P. N. (2019). Design, synthesis, and biological evaluation of 1,8-naphthyridine glucosamine conjugates as antimicrobial agents. Drug Development Research, 80(1), 179-186. https://doi.org/10.1002/ddr.21508
Mohammed AAM, et al. Design, Synthesis, and Biological Evaluation of 1,8-naphthyridine Glucosamine Conjugates as Antimicrobial Agents. Drug Dev Res. 2019;80(1):179-186. PubMed PMID: 30570767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis, and biological evaluation of 1,8-naphthyridine glucosamine conjugates as antimicrobial agents. AU - Mohammed,Aya A M, AU - Suaifan,Ghadeer A R Y, AU - Shehadeh,Mayadah B, AU - Okechukwu,Patrick N, Y1 - 2018/12/20/ PY - 2018/10/31/received PY - 2018/12/04/revised PY - 2018/12/05/accepted PY - 2018/12/21/pubmed PY - 2019/6/7/medline PY - 2018/12/21/entrez KW - 1,8-napthyridine KW - antimicrobial KW - carboxamide KW - glucosamine KW - nalidixic acid KW - resistant bacteria SP - 179 EP - 186 JF - Drug development research JO - Drug Dev. Res. VL - 80 IS - 1 N2 - 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. SN - 1098-2299 UR - https://www.unboundmedicine.com/medline/citation/30570767/Design_synthesis_and_biological_evaluation_of_18_naphthyridine_glucosamine_conjugates_as_antimicrobial_agents_ L2 - https://doi.org/10.1002/ddr.21508 DB - PRIME DP - Unbound Medicine ER -