Synthesis and Structural Activity Relationship Study of Antitubercular Carboxamides

Ugwu, David I.; Ezema, Benjamin E.; Eze, Florence Uchenna; Ugwuja, Daniel I.

doi:10.1155/2014/614808

Cited by 17 publications

(13 citation statements)

References 68 publications

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“…Carboxamides are ubiquitous in their function in drug molecules as a pharmacophore (Montalbetti and Falque, 2005). Carboxamides have been reported as antihelmintic (Ugwu et al, 2018a), antitubercular (Ugwu et al, 2014) anti-trypanosomal (Ugwu et al, 2018b) agents. They are also present in drug molecules used in the blockage of cholesterol synthesis (Graul and Castaner, 1997), treatment of hypertension and andina (Ananthanarayanan et al, 1993), blockade of angiotensin-II receptors (deGasparo and Whitebread, 1995), inhibition of angiotensin converting enzymes (Patchett, 1993), treatment of HIV (Roskoski, 2003), and management of heart disease (Hogan et al, 2000), to mention but a few.…”

Section: Introductionmentioning

confidence: 99%

Biological Activity Evaluation of Some New Benzenesulphonamide Derivatives

et al. 2019

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Bacterial resistance to antibiotics has become one of the most challenging problems of infectious disease treatment. Ten new derivatives of benzenesulphonamide bearing carboxamide functionality were synthesized and investigated for their in vivo anti-inflammatory, in vitro anti-microbial and anti-oxidant activities. The base promoted reactions of the appropriate amino acids with substituted benzenesulphonyl chlorides gave the benzene sulphonamides (3a-j) in excellent yields. Palladium mediated amidation of the benzenesulphonamides (3a-j) and butylamine gave the new carboxamides (4a-j) in excellent yield. Compounds 4a and 4c inhibited carrageenan induced rat-paw edema at 94.69, 89.66, and 87.83% each at 1, 2, and 3 h, respectively. In the antimicrobial activity, compound 4d (MIC 6.72 mg/mL) was most potent against E. coli, compound 4h (MIC 6.63 mg/mL) was the most active against S. aureus, compound 4a (MIC 6.67 and 6.45 mg/mL) was most active against P. aeruginosa and S. typhi, respectively, compound 4f (MIC 6.63 mg/mL) was the most active against B. subtilis, compounds 4e and 4h (MIC 6.63 mg/mL) each were the most active against C. albicans, while compound 4e (MIC 6.28 mg/mL) was most active against A. niger. Only compound 4e (IC50 0.3287 mg/mL) had comparable activity with Vitamin C (IC50 0.2090 mg/mL).

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Section: Introductionmentioning

confidence: 99%

Biological Activity Evaluation of Some New Benzenesulphonamide Derivatives

et al. 2019

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“…They have reported the inhibitory properties of these compounds towards Mycobacteria at concentrations of 50-100 µg/ml. Ugwu et al have also shown that the inhibitory concentrations of carboxamides against MT is in the range of 25-50 µg/ml [23] . Cho et al showed that the inhibitory concentrations of EGCG against the antibiotic resistant Imipenem Klebsiella pneumonia strains to be in the range of 300-650 µg/ml [12] .…”

Section: Resultsmentioning

confidence: 97%

Epigallocatechin Gallate, a Green Tea Polyphenol Inhibits Mycobacterium smegmatis: In silico and In vitro Studies

Narayanan¹,

Ramesh²

2017

pharmaceutical-sciences

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Narayanan and Ramesh: Epigallocatechin Gallate Inhibits M. smegmatisPresence of multidrug resistant strains makes treatment of tuberculosis difficult. Conventional frontline antituberculosis therapy has high incidence of treatment failure due to non-adherence and severe side effects, and therefore warrants alternative approaches using safe, natural compounds. (-) Epigallocatechin gallate, a green tea catechin with significant antimicrobial properties, and its derivatives have been studied for their inhibitory effects on Mycobacterium smegmatis. Enoyl reductase (Inh A, PDB ID: 2NV6), an important drug target inhibited by the antituberculosis drug, isoniazid, was docked with geometrically optimized conformation of epigallocatechin gallate and two of its derivatives using AutoDock software. Perpropionate and permethyl derivatives of epigallocatechin gallate were synthesized and, along with epigallocatechin gallate, evaluated for their inhibitory and cytotoxic properties against M. smegmatis using microplate dilution method and alamarBlue® assay, respectively. Ames test was performed to assess the mutagenic potential of epigallocatechin gallate. It was docked successfully onto the InhA with docking energy of -9.38 kcal mol -1 . Analysis of neighbouring groups revealed 11 amino acid residues common to both isoniazid and epigallocatechin gallate. The minimum inhibitory concentrations for epigallocatechin gallate, perpropionate and permethyl were found to be 128 (58.2% inhibition), 8 (32.9%) and 4 (12.5%) µg/ml, respectively. Epigallocatechin gallate showed a cytotoxicity of 18.6% at a concentration of 8 µg/ml, while the two derivatives did not show any toxicity, even at 64 µg/ml. Ames test revealed the absence of mutagenicity for epigallocatechin gallate, in presence and absence of metabolic activation. Nonmutagenic epigallocatechin gallate inhibits the growth of M. smegmatis and warrants further investigation as an adjunct therapy for pathogenic mycobacteria.

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“…Appropriate substituted benzenesulfonyl chloride (1ac, 1.82 mmol) was added in portions for 1 h to an aqueous solution of L-leucine (1.5 mmol) containing sodium carbonate (Na 2 CO 3 , 1.82 mmol) at −5 • C. The slurry formed was stirred at room temperature for 4 h (TLC (MeOH/DCM, 1:9 monitored). The mixture was acidified to pH 2 (Ugwu et al, 2014;Ezugwu et al, 2020).…”

Section: General Procedures For the Synthesis Of Substituted Benzenesumentioning

confidence: 99%

“…Carboxamides are also ubiquitous functionality GRAPHICAL ABSTRACT | in medicate particles as pharmacophores (Montalbetti and Falque, 2005). Carboxamides have been accounted for as antimicrobial and antioxidant (Eze et al, 2019), carbonic anhydrase enzyme inhibitor and antioxidant (Deniz et al, 2019), anticancer (Kumar et al, 2009), anthelmintic (Ugwu et al, 2018a), antitubercular (Ugwu et al, 2014), antitrypanosomal (Ugwu et al, 2018b), and anti-inflammatory and analgesic (Ugwu et al, 2018c) agents. Day and Greenfield (2004) reported that peptides are resourceful pharmacophores as they play important roles within the physical body and other organisms.…”

Section: Introductionmentioning

confidence: 99%

Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking

et al. 2020

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The increase of antimicrobial resistance (AMR) and antimalarial resistance are complex and severe health issues today, as many microbial strains have become resistant to market drugs. The choice for the synthesis of new dipeptide-carboxamide derivatives is as a result of their wide biological properties such as antimicrobial, anti-inflammatory, and antioxidant activities. The condensation reaction of substituted benzenesulphonamoyl pentanamides with the carboxamide derivatives using peptide coupling reagents gave targeted products (8a-j). The in silico antimalarial and antibacterial studies showed good interactions of the compounds with target protein residues and a higher dock score in comparison with standard drugs. In the in vivo study, compound 8j was the most potent antimalarial agent with 61.90% inhibition comparable with 67% inhibition for Artemisinin. In the in vitro antimicrobial activity, compounds 8a and 8b (MIC 1.2 × 10−3 M and 1.1 × 10−3 M) were most potent against S. aureus; compound 8a, 8b, and 8j with MIC 6.0 × 10−3 M, 5.7 × 10−4 M, and 6.5 × 10−4 M, respectively, were the most active against B. subtilis; compound 8b (MIC 9.5 × 10−4 M) was most active against E.coli while 8a, 8b and 8d were the most active against S. typhi. Compounds 8c and 8h (MIC 1.3 × 10−3 M) each were the most active against C. albicans, while compound 8b (MIC 1.3 × 10−4 M) was most active against A. niger.

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Synthesis and Structural Activity Relationship Study of Antitubercular Carboxamides

Cited by 17 publications

References 68 publications

Biological Activity Evaluation of Some New Benzenesulphonamide Derivatives

Biological Activity Evaluation of Some New Benzenesulphonamide Derivatives

Epigallocatechin Gallate, a Green Tea Polyphenol Inhibits Mycobacterium smegmatis: In silico and In vitro Studies

Novel Leu-Val Based Dipeptide as Antimicrobial and Antimalarial Agents: Synthesis and Molecular Docking

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