Synthesis, molecular modeling, quantum mechanical calculations and ADME estimation studies of benzimidazole-oxadiazole derivatives as potent antifungal agents

Çevik, Ulviye Acar; Çeli̇k, İsmail; Işık, Ayşen; Pillai, Renjith Raveendran; Tallei, Trina Ekawati; Yadav, Rohitash; Özkay, Yusuf; Kaplancıklı, Zafer Asım

doi:10.1016/j.molstruc.2021.132095

Cited by 28 publications

(11 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The antifungal activity of final compounds ( 6a – 6l ) was screened against four fungal strains according to the standard procedure of CLSI as described in the previous study C.…”

Section: Methodsmentioning

confidence: 99%

“…The antifungal activity of final compounds ( 6a – 6l ) was screened against four fungal strains according to the standard procedure of CLSI as described in the previous study. 44 C. albicans (ATCC 24433), C. krusei (ATCC 6258), C. parapsilopsis (ATCC 22019), and C. glabrata (ATCC 9) were used to test the antifungal activity of the final compounds. Voriconazole and fluconazole (against candida strains) were used as standard reference drugs.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

et al. 2023

Self Cite

View full text Add to dashboard Cite

Invasive fungal infections (IFIs) are increasing as major infectious diseases around the world, and the limited efficacy of existing medications has resulted in substantial morbidity and death in patients due to the lack of effective antifungal agents and serious drug resistance. In this study, a series of benzimidazole-1,2,4-triazole derivatives (6a−6l) were synthesized and characterized by 1 H NMR, 13 C NMR, and HR-MS spectral analysis. All the target compounds were screened for their in vitro antifungal activity against four fungal strains, namely, C. albicans, C. glabrata, C. krusei, and C. parapsilopsis. The synthesized compounds exhibited significant antifungal potential, especially against C. glabrata. Three compounds (6b, 6i, and 6j) showed higher antifungal activity with their MIC values (0.97 μg/mL) compared with voriconazole and fluconazole. Molecular docking provided a possible binding mode of compounds 6b, 6i, and 6j in the 14α-demethylase active site. Our studies suggested that the benzimidazole-1,2,4-triazole derivatives can be used as a new fungicidal lead targeting 14α-demethylase for further structural optimization. In addition, their effects on the L929 cell line were also investigated to evaluate the cytotoxic effects of the compounds. SEM analyses were performed to examine the effects of compounds 6a, 6i, and 6j on C. glabrata cells under in vivo experimental conditions.

show abstract

“…The antifungal activity of final compounds ( 6a – 6l ) was screened against four fungal strains according to the standard procedure of CLSI as described in the previous study C.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…To evaluate the stability of the protein–ligand complexes formed by the potential antifungal compounds 5c and 5f with Candida sterol 14-α demethylase, 100 ns duration MD simulations were performed. , Also, the complex of the standard compound voriconazole with CYP51 was simulated for MD validation and compared with the complexes with synthesized compounds 5c and 5f (Figure S2). Charmm36m force fields for topology files of CYP51 and compounds 5c and 5f were chosen to be compatible with protein–ligand complexes containing the heme structure.…”

Section: Results and Discussionmentioning

confidence: 99%

“…The interactions of compounds 5a – h , which consist of a substituted thiadiazole derivative bridged to the benzimidazole 2-position by a phenyl group and show good antifungal activity, with the target Candida sterol 14-α demethylase (CYP51) were analyzed by the in silico molecular docking method. On the basis of previous studies, benzimidazole derivative compounds show antifungal activity by inhibiting this enzyme. − For this reason, CYP51 was identified as the target protein. The azole group of antifungal compounds such as fluconazole and voriconazole is responsible for the interaction with the heme structure in the CYP51 structure, and this interaction is key for inhibition …”

Section: Results and Discussionmentioning

confidence: 99%

Synthesis, Molecular Docking, Dynamics, Quantum-Chemical Computation, and Antimicrobial Activity Studies of Some New Benzimidazole–Thiadiazole Hybrids

et al. 2022

Self Cite

View full text Add to dashboard Cite

In this study, some new compounds, which are 2aminothiadiazole derivatives linked by a phenyl bridge to the 2position of the benzimidazole ring, were designed and synthesized as antimicrobial agents. The structures of the compounds were elucidated by 1 H and 13 C NMR spectroscopy, high-resolution mass spectrometry, and elemental analysis. The antifungal activities of the synthesized compounds were tested on Candida albicans, Candida krusei, Candida glabrata, and Candida parapsilosis. Compound 5f is more active against C. albicans and C. glabrata than standard fluconazole and varicanazole. Compounds were also evaluated for their counteracting activity against Gram-positive Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, and Pseudomonas aeruginosa and Gram-negative Enterococcus faecalis, Bacillus subtilis, and Staphylococcus aureus. Compounds 5c and 5h had minimum inhibitory concentrations against E. faecalis close to that of the standard azithromycin. Molecular docking studies were performed against Candida species' 14-α demethylase enzyme. 5f was the most active compound against Candida species, which gave the highest docking interaction energy. The stabilities of compounds 5c and 5f with CYP51 were tested using 100 ns molecular dynamics simulations. According to the theoretical ADME calculations, the profiles of the compounds are suitable in terms of limiting rules. HOMO−LUMO analysis showed that 5h is chemically more reactive (represented with the lower ΔE = 3.432 eV) than the other molecules, which is compatible with the highest antibacterial activity result.

show abstract

“…synthesised a series of 1,3,4-oxadiazole derivatives and screened the synthesised compounds for their antifungal activity against Candida glabrata , Candida cruzi , Candida parapsilosis and Candida albicans . The results showed that compounds 45a (MIC 50 = 0.78 μg/mL, Figure 4 ) and 45b (MIC 50 = 0.78 μg/mL, Figure 4 ) had better inhibitory activity against Candida albicans than that of Ketoconazole (MIC 50 = 1.56 μg/mL) 51 .…”

Section: Oxadiazolementioning

confidence: 99%

Research progress on the synthesis and pharmacology of 1,3,4-oxadiazole and 1,2,4-oxadiazole derivatives: a mini review

Wang

Sun

Jia

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

Oxadiazole is a five-membered heterocyclic compound containing two nitrogen atoms and one oxygen atom. The 1,3,4-oxadiazole and 1,2,4-oxadiazole have favourable physical, chemical, and pharmacokinetic properties, which significantly increase their pharmacological activity via hydrogen bond interactions with biomacromolecules. In recent years, oxadiazole has been demonstrated to be the biologically active unit in a number of compounds. Oxadiazole derivatives exhibit antibacterial, anti-inflammatory, anti-tuberculous, anti-fungal, anti-diabetic and anticancer activities. In this paper, we report a series of compounds containing oxadiazole rings that have been published in the last three years only (2020–2022) as there was no report or their activities described in any article in 2019, which will be useful to scientists in research fields of organic synthesis, medicinal chemistry, and pharmacology.

show abstract

Synthesis, molecular modeling, quantum mechanical calculations and ADME estimation studies of benzimidazole-oxadiazole derivatives as potent antifungal agents

Cited by 28 publications

References 56 publications

Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

Synthesis, Molecular Docking, Dynamics, Quantum-Chemical Computation, and Antimicrobial Activity Studies of Some New Benzimidazole–Thiadiazole Hybrids

Research progress on the synthesis and pharmacology of 1,3,4-oxadiazole and 1,2,4-oxadiazole derivatives: a mini review

Contact Info

Product

Resources

About