TY - JOUR
T1 - Towards eradicating antibiotic-resistant bacteria
T2 - Synthesis and antibacterial activities of substituted N-(2-nitrophenyl)pyrrolidine- and piperidine-2-carboxylic acids
AU - Odusami, Jocelyn A.
AU - Ikhile, Monisola I.
AU - Fotsing, Marthe C.D.
AU - Olasupo, Idris A.
AU - Izunobi, Josephat U.
AU - Bamgbade, Elizabeth O.
AU - Fonkui, Thierry Y.
AU - Asekun, Olayinka T.
AU - Familoni, Oluwole B.
AU - Ndinteh, Derek T.
N1 - Publisher Copyright:
© 2019 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University.
PY - 2019
Y1 - 2019
N2 - Antibacterial resistance is a source of great concern in the effective prevention and treatment of infections caused by bacteria, making the development of requisite therapeutics a major challenge. N-(Nitrophenyl)cycloamino acids are important compounds in the synthesis of poly-condensed nitrogen-containing heterocycles with marked activities in many biological systems. A series of substituted N-(o-nitrophenyl)cycloamino-2-carboxylic acids 3a-3g were synthesized via the condensation reaction of substituted o-halogenonitrobenzenes with L-proline 2a and D,L-pipecolinic acid 2b, under refluxing alcoholic basic conditions in excellent yields. The synthesized compounds were characterised by FT-IR, (1H & 13C) NMR, UV-Vis, mass spectroscopy and elemental analysis. Their antibacterial activities were evaluated against five Gram-positive and five Gram-negative bacterial strains using the broth micro-dilution procedure. The antibacterial activities of the synthesized compounds were compared with streptomycin and nalidixic acid as standard antibiotic drugs. The minimum inhibitory concentration (MIC) values of compounds 3a-3g revealed good antibacterial activities against the tested microorganisms. Compounds 3a-3g were more potent than nalidixic acid against Enterococcus faecalis, Mycobacterium smegmatis, Escherichia coli and Proteus vulgaris and also more potent than streptomycin against Enterobacter cloacae and Staphylococcus aureus. Compounds 3a, 3c and 3g displayed the highest antibacterial potency with an MIC value of 15.6 μg/mL against E. cloacae, E. faecalis and P. mirabilis, respectively. These results indicated that these aryl cycloamino acids with antibacterial activities had potential applications as substitutes for antimicrobial peptide antibiotics, which are not susceptible to bacterial resistance, to solve the problem of drug resistance.
AB - Antibacterial resistance is a source of great concern in the effective prevention and treatment of infections caused by bacteria, making the development of requisite therapeutics a major challenge. N-(Nitrophenyl)cycloamino acids are important compounds in the synthesis of poly-condensed nitrogen-containing heterocycles with marked activities in many biological systems. A series of substituted N-(o-nitrophenyl)cycloamino-2-carboxylic acids 3a-3g were synthesized via the condensation reaction of substituted o-halogenonitrobenzenes with L-proline 2a and D,L-pipecolinic acid 2b, under refluxing alcoholic basic conditions in excellent yields. The synthesized compounds were characterised by FT-IR, (1H & 13C) NMR, UV-Vis, mass spectroscopy and elemental analysis. Their antibacterial activities were evaluated against five Gram-positive and five Gram-negative bacterial strains using the broth micro-dilution procedure. The antibacterial activities of the synthesized compounds were compared with streptomycin and nalidixic acid as standard antibiotic drugs. The minimum inhibitory concentration (MIC) values of compounds 3a-3g revealed good antibacterial activities against the tested microorganisms. Compounds 3a-3g were more potent than nalidixic acid against Enterococcus faecalis, Mycobacterium smegmatis, Escherichia coli and Proteus vulgaris and also more potent than streptomycin against Enterobacter cloacae and Staphylococcus aureus. Compounds 3a, 3c and 3g displayed the highest antibacterial potency with an MIC value of 15.6 μg/mL against E. cloacae, E. faecalis and P. mirabilis, respectively. These results indicated that these aryl cycloamino acids with antibacterial activities had potential applications as substitutes for antimicrobial peptide antibiotics, which are not susceptible to bacterial resistance, to solve the problem of drug resistance.
KW - Antibiotics
KW - Bacteria
KW - Cyclic amino acids
KW - o-Halogenonitrobenzene
UR - http://www.scopus.com/inward/record.url?scp=85075864499&partnerID=8YFLogxK
U2 - 10.5246/jcps.2019.10.067
DO - 10.5246/jcps.2019.10.067
M3 - Article
AN - SCOPUS:85075864499
SN - 1003-1057
VL - 28
SP - 704
EP - 715
JO - Journal of Chinese Pharmaceutical Sciences
JF - Journal of Chinese Pharmaceutical Sciences
IS - 10
ER -