Design, molecular docking, and antimicrobial assessment of newly synthesized phytochemical thymol Mannich base derivatives

Bishoyi, Ajit Kumar; Mahapatra, Monalisa; Paidesetty, Sudhir Kumar; Padhy, Rabindra N.

doi:10.1016/j.molstruc.2021.130908

Cited by 17 publications

(7 citation statements)

References 28 publications

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“…The observed molecular interactions were essentially hydrophobic [ 26 ]. Some authors have identified that thymol can interact with dihydro-folate reductase from S. aureus [ 27 , 28 ]. Barbosa et al (2021) determined that thymol can also inhibit NorA efflux pump inhibition in multidrug-resistant (MDR) S. aureus strains.…”

Section: Resultsmentioning

confidence: 99%

In Silico Evaluation of the Antimicrobial Activity of Thymol—Major Compounds in the Essential Oil of Lippia thymoides Mart. & Schauer (Verbenaceae)

et al. 2022

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In this paper, we evaluated the drug-receptor interactions responsible for the antimicrobial activity of thymol, the major compound present in the essential oil (EO) of Lippia thymoides (L. thymoides) Mart. & Schauer (Verbenaceae). It was previously reported that this EO exhibits antimicrobial activity against Candida albicans (C. albicans), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli). Therefore, we used molecular docking, molecular dynamics simulations, and free energy calculations to investigate the interaction of thymol with pharmacological receptors of interest to combat these pathogens. We found that thymol interacted favorably with the active sites of the microorganisms’ molecular targets. MolDock Score results for systems formed with CYP51 (C. albicans), Dihydrofolate reductase (S. aureus), and Dihydropteroate synthase (E. coli) were −77.85, −67.53, and −60.88, respectively. Throughout the duration of the MD simulations, thymol continued interacting with the binding pocket of the molecular target of each microorganism. The van der Waals (ΔEvdW = −24.88, −26.44, −21.71 kcal/mol, respectively) and electrostatic interaction energies (ΔEele = −3.94, −11.07, −12.43 kcal/mol, respectively) and the nonpolar solvation energies (ΔGNP = −3.37, −3.25, −2.93 kcal/mol, respectively) were mainly responsible for the formation of complexes with CYP51 (C. albicans), Dihydrofolate reductase (S. aureus), and Dihydropteroate synthase (E. coli).

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Section: Resultsmentioning

confidence: 99%

In Silico Evaluation of the Antimicrobial Activity of Thymol—Major Compounds in the Essential Oil of Lippia thymoides Mart. & Schauer (Verbenaceae)

et al. 2022

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“…[58] Moreover, recent study conducted by Cruz et al [59] stipulated that thymol, as a major compound in Lippia thymoides (EO), exhibited antimicrobial activity against (C. albicans) by targeting the CYP51. Furthermore, a study performed by Bishoyi et al [60] showed that a thymol derivate congener (4-((4-hydroxy-5-isopropyl-2-methylbenzyl)amino)-N- (5-methylisoxazol-3-yl) benzene sulfonamide had a high docking score at (À 9.5) kcal/mol against the fungal target (CYP51).…”

Section: In Silico Evaluation Of Carvacrol and Thymol Antifungal Prop...mentioning

confidence: 99%

Combined in vitro/in silico approaches, molecular dynamics simulations and safety assessment of the multifunctional properties of thymol and carvacrol: A comparative insight

Akermi,

Smaoui,

Chaari

et al. 2024

Chemistry & Biodiversity

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Bioactive compounds derived from medicinal plants have acquired immense attentiveness in drug discovery and development. The present study investigated in vitro and predicted in silico the antibacterial, antifungal, and antiviral properties of thymol and carvacrol, and assessed their safety. The performed microbiological assays against Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica Typhimurium revealed that the minimal inhibitory concentration values ranged from (0.078 to 0.312 mg/mL) and the minimal fungicidal concentration against Candida albicans was 0.625 mg/mL. Molecular docking simulations, stipulated that these compounds could inhibit bacterial replication and transcription functions by targeting DNA and RNA polymerases receptors with docking scores varying between (‐5.1 to ‐6.9 kcal/mol). Studied hydroxylated monoterpenes could hinder C. albicans growth by impeding lanosterol 14α‐demethylase enzyme and showed a (ΔG = ‐6.2 and ‐6.3 kcal/mol). Computational studies revealed that thymol and carvacrol could target the SARS‐Cov‐2 spike protein of the Omicron variant RBD domain. Molecular dynamics simulations disclosed that these compounds have a stable dynamic behavior over 100 ns as compared to remdesivir. Chemo‐computational toxicity prediction using Protox II webserver indicated that thymol and carvacrol could be safely and effectively used as drug candidates to tackle bacterial, fungal, and viral infections as compared to chemical medication.

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“…The combination of sulfonamide with the heterocycles viz., thymol, cumene, indazole, pyrazole, pyridazines, triazoles, and coumarins have been successful in the pharma market and still, some of them are under clinical trials. [21][22][23] Sulfonamides along with coumarin scaffold could be utilized for various types of anticancer activity as suggested by the coherent study findings of Claudiu T. Supuran's group, Pingaew et al [24] and Wang et al [25] All the studies investigated the crucial roles of the potent sulfonamide pharmacophore moieties at the terminal position such as phenyl pyrazolyl, pyridyl, and pyrimidinyl (substituted with methyl and methoxy) for their anticancer and antiproliferative activity, and the results showed significant activity; however, the pyrimidinyl substituted with methoxy-or dimethoxy-bearing compounds at the terminal position has been deduced to be the most potent analog among all. [24,25] The most prevalent scope of exploring the sulfonamides is its flexibility and adaptability toward different pharmacophores since its discovery through the drug Prontosil.…”

Section: Coumarin-sulfonamide As a Core Ring For Anticancer Drug Deve...mentioning

confidence: 99%

Coumaryl‐sulfonamide moiety: Unraveling their synthetic strategy and specificity toward hCA IX/XII, facilitating anticancer drug development

Mahapatra

Mekap

Mal

et al. 2023

Archiv der Pharmazie

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Currently, cancer is the most grieving threat to society. The cancer-related death rate has had an ascending trend, despite the implementation of numerous treatment strategies or the discovery of an array of potent molecules against several pathways of cancer growth. The need of the hour is to prevent the multidrug resistance toll, and the current efforts have been bestowed upon a versatile small molecule scaffold, coumarin (benz[α]pyrone), a natural compound possessing interesting affinity toward the cancer target human carbonic anhydrase (hCA), focusing on hCA I, II, IX, and XII. Along with coumarin, the age-old known antibacterial drug sulfonamide, when conjugated at positions 3, 7, and 8 of coumarin either with a linker group or as a single entity, has been reported to enhance the affinity of coumarin toward the overexpressed enzymes in tumor cell lines. The sulfonamides have been listed as obsolete drugs due to the severe side effects caused by them; however, their affinity toward the hCA-zinc-binding core has attracted the attention of researchers. Hence, in the process of drug development, coumarin and sulfonamides have remained the choice of last resort. To unveil the synthetic strategy of coumarin-sulfonamide conjugation, their rationale for inhibiting cancer cells/enzymes, and their affinity toward various types of carcinoma have been the sole goal of the researchers. This review specifically focuses on the mechanism of action and the structure-activity relationship through synthetic strategies and the binding affinity of coumarylsulfonamide conjugates with the anticancer targets possessing the highest enzyme affinity, since 2008.

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Design, molecular docking, and antimicrobial assessment of newly synthesized phytochemical thymol Mannich base derivatives

Cited by 17 publications

References 28 publications

In Silico Evaluation of the Antimicrobial Activity of Thymol—Major Compounds in the Essential Oil of Lippia thymoides Mart. & Schauer (Verbenaceae)

In Silico Evaluation of the Antimicrobial Activity of Thymol—Major Compounds in the Essential Oil of Lippia thymoides Mart. & Schauer (Verbenaceae)

Combined in vitro/in silico approaches, molecular dynamics simulations and safety assessment of the multifunctional properties of thymol and carvacrol: A comparative insight

Coumaryl‐sulfonamide moiety: Unraveling their synthetic strategy and specificity toward hCA IX/XII, facilitating anticancer drug development

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