New peptide derived antimalaria and antimicrobial agents bearing sulphonamide moiety

Ugwuja, Daniel I.; Okoro, Uchechukwu C.; Soman, Shubhangi S.; Soni, Rina; Okafor, Sunday N.; Ugwu, David I.

doi:10.1080/14756366.2019.1651313

Cited by 18 publications

(15 citation statements)

References 33 publications

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“…Based on the fact that the pathophysiology mechanism through which plasmodia cause malaria results in cell oxidative stress, efforts are currently channelled to discovering agents with dual antiplasmodial and antioxidant activities [ 26 , 27 , 38 ]. The compounds were screened in vitro against chloroquine sensitive strains of P .…”

Section: Resultsmentioning

confidence: 99%

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New sulphonamide pyrolidine carboxamide derivatives: Synthesis, molecular docking, antiplasmodial and antioxidant activities

et al. 2021

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Carboxamides bearing sulphonamide functionality have been shown to exhibit significant lethal effect on Plasmodium falciparum, the causative agent of human malaria. Here we report the synthesis of thirty-two new drug-like sulphonamide pyrolidine carboxamide derivatives and their antiplasmodial and antioxidant capabilities. In addition, molecular docking was used to check their binding affinities for homology modelled P. falciparum N-myristoyltransferase, a confirmed drug target in the pathogen. Results revealed that sixteen new derivatives killed the parasite at single-digit micromolar concentration (IC50 = 2.40–8.30 μM) and compounds 10b, 10c, 10d, 10j and 10o scavenged DPPH radicals at IC50s (6.48, 8.49, 3.02, 6.44 and 4.32 μg/mL respectively) comparable with 1.06 μg/mL for ascorbic acid. Compound 10o emerged as the most active of the derivatives to bind to the PfNMT with theoretical inhibition constant (Ki = 0.09 μM) comparable to the reference ligand pyrazole-sulphonamide (Ki = 0.01 μM). This study identifies compound 10o, and this series in general, as potential antimalarial candidate with antioxidant activity which requires further attention to optimise activity.

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Section: Resultsmentioning

confidence: 99%

“…In this present work, we continued our search for new antimalarial lead that possesses antioxidant effect in the sulphonamide-carboxamide series [ 26 , 27 ] and in addition tested their capability to bind to P . falciparum NMT (PfNMT); a validated antimalarial drug target.…”

Section: Introductionmentioning

confidence: 99%

New sulphonamide pyrolidine carboxamide derivatives: Synthesis, molecular docking, antiplasmodial and antioxidant activities

et al. 2021

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“…The animal ethics committee, Veterinary Medicine Department, University of Nigeria, Nsukka gave permission and approval for the use of animals in this experiment (PG/PhD/16/80697). The percentage inhibition of parasite was calculated from the equation [(A-B)/A] × 100 (Ugwuja et al, 2019;Ezugwu et al, 2020); where A = parasitemia of the untreated group and B = parasitemia of the tested group. In this study, the compounds with the percentage inhibition below 30 are inactive, 30-40 are partially active, and 40 and above are regarded to be active.…”

Section: In Vivo Antimalarialmentioning

confidence: 99%

“…In a continuation of our work, we synthesized novel Leu-Val dipeptide carboxamide scaffolds bearing sulfonamide moieties with potent antimalarial and antimicrobial properties. The quest for leu-val combination skeleton was as a result of antimalarial properties of ala-gly dipeptides (Ugwuja et al, 2019), antimalarial and antioxidant property of val-val dipeptides by Ezugwu et al (2020), and also an antimalarial property of quinine derivatives containing some amino acid, dipeptide, or tripeptide (Panda et al, 2013).…”

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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“…The stress leads to molecular and cellular damage which is implicated in many disease conditions like cancer, bacterial infections and aging. Therefore, drug candidates with antiplasmodial potency that can scavenge oxygen free radicals are highly sought after in antimalarial development [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, molecular docking, antiplasmodial and antioxidant activities of new sulfonamido-pepetide derivatives

Onoabedje

Ibezim

Okoro

et al. 2020

Heliyon

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Twenty-three new series of toluene-sulfonamide dipeptide derivatives were synthesized and screened for antiplasmodial and antioxidant potencies. Many of the derivatives were active against Plasmodium falciparum with IC 50 ranging from 3.20 – 9.10 μM. The ability of compounds 7h , 7m and 7n (IC 50 of 7.53, 7.21 and 6.01 μg/mL respectively) to scavenge DPPH free radicals were comparable to that of ascorbic acid. Additionally, molecular docking disclosed that four compounds exhibited theoretical inhibition constant at submicromolar concentrations ( K i = 0.72, 0.75, 0.57, and 0.53 μM respectively) compare to the reference ligand (a pyrazole sulfonamide; K i = 0.01 μM). Overall, some of the derivatives possess antimalarial property as well as the ability to inhibit oxidative stress in malaria pathophysiology; and hence, are good candidates for further antimalarial drug research.

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New peptide derived antimalaria and antimicrobial agents bearing sulphonamide moiety

Cited by 18 publications

References 33 publications

New sulphonamide pyrolidine carboxamide derivatives: Synthesis, molecular docking, antiplasmodial and antioxidant activities

New sulphonamide pyrolidine carboxamide derivatives: Synthesis, molecular docking, antiplasmodial and antioxidant activities

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

Synthesis, molecular docking, antiplasmodial and antioxidant activities of new sulfonamido-pepetide derivatives

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