Design, synthesis and evaluation of benzoheterocycle analogues as potent antifungal agents targeting CYP51

Zhao, Shizhen; Peng, Wei; Wu, Mengya; Zhang, Xiangqian; Zhao, Liyu; Jiang, Xiangyu; Hao, Chenzhou; X, Su; Cheng, Maosheng

doi:10.1016/j.bmc.2018.04.054

Cited by 26 publications

(14 citation statements)

References 24 publications

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“…The advanced docking program, AutoDock Vina was used to evaluate the binding properties of test compounds into microbial targets [31]. The crystal structures of a ternary complex of E. coli dihydropteroate Thakral and Singh synthase (1aj0) [32] and sterol 14-alpha-demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole (5fsa) [33,34] were downloaded from the protein data bank (www.rcsb.org). All bound water molecules and cocrystallized ligands were removed from protein, and polar hydrogen atoms were added.…”

Section: Molecular Modelingmentioning

confidence: 99%

Biological Evaluation, Qsar and Molecular Modeling Studies of 2,4-Dichlorobenzoic Acid Derivatives as Antimicrobial Agents

Thakral

Singh

2019

Asian J Pharm Clin Res

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Objective: The aim of this study was to evaluate 2,4-dichlorobenzoic acid derivatives as antimicrobial agents through in vitro, QSAR and molecular docking studies. Methods: The compounds were subjected to in vitro antimicrobial screening by test tube dilution method and the structural characteristics governing the antimicrobial potential were studied using QSAR methodology. These compounds were also screened for docking simulation to find out binding confirmation of reported compounds with PDB 1aj0 and 5fsa using AutoDock tools and discovery studio. Results: The antimicrobial evaluation data indicated that compounds 13 and 18 were found to be the most effective against all the bacterial strains and Aspergillus niger while compounds 1 and 14 exhibited more antifungal potential against Candida albicans. QSAR studies confirmed the role of molar refractivity and Balaban index (J) as controlling parameters for antimicrobial potential. Molecular modeling study revealed that compounds interact with the active site of PDB by hydrophobic, hydrogen bonding, and Van der Wall interactions. Conclusion: These test compounds were identified as potent candidates for the control of microbial strains tested, and structural relationship with activity may provide valuable information for further design and synthesis of compounds with antimicrobial potential.

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Section: Molecular Modelingmentioning

confidence: 99%

Biological Evaluation, Qsar and Molecular Modeling Studies of 2,4-Dichlorobenzoic Acid Derivatives as Antimicrobial Agents

Thakral

Singh

2019

Asian J Pharm Clin Res

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“…Series of amidoesters substituted with imidazolylmethyl groups were reported to have bioactivity against opportunistic fungal pathogens Candida albicans , Candida tropicalis , Cryptococcus neoformans , and Aspergillus fumigatus [ 77 , 78 ]. Some of these compounds, including 100 [ 77 ] and 101 [ 78 ] ( Figure 11 a) displayed better antifungal properties than fluconazole 21 (cf. Figure 2 ).…”

Section: Sterolome-informed Antimicrobial Targetsmentioning

confidence: 99%

“…The sterols of C. albicans administered with these compounds were analyzed to confirm a mechanism of disrupting ergosterol biosynthesis. Ergosterol normally comprises of the vast majority of the sterol profile in C. albicans (>98%), and treatment with 100 [ 77 ] or 101 [ 78 ] reduced ergosterol in a dose dependent manner. Dose-dependent increases in lanosterol 12 were noted, as well as increases in 14α-methylsterol by-products eburicol 102 and obtusifoliol 31 ( Figure 11 a).…”

Section: Sterolome-informed Antimicrobial Targetsmentioning

confidence: 99%

“…Dose-dependent increases in lanosterol 12 were noted, as well as increases in 14α-methylsterol by-products eburicol 102 and obtusifoliol 31 ( Figure 11 a). The increase in lanosterol (substrate for C. albicans 14-SDM), the increase in 14-methylsterols, and a commensurate decrease in ergosterol itself, suggested 14-SDM as a target for these molecules [ 77 , 78 ].…”

Section: Sterolome-informed Antimicrobial Targetsmentioning

confidence: 99%

“…Red arrows signify increase or decrease in sterols within the profile of inhibited cultures relative to non-inhibited cultures. ( a ) Oxazole amidoester-treated cultures of C. albicans decrease in ergosterol and increase in lanosterol and by-products obtusifoliol and eburicol, indicating disruption of 14-SDM activity [ 77 , 78 ]. ( b ) Posaconazole-treated cultures of Rhizopus arrhizus decrease in ergosterol and ergosta-5,7-dienol and increase in lanosterol, obtusifoliol, and eburicol, and produce toxic 14-methylergosta-8,24(28)-dien-3β,6α-diol [ 79 ].…”

Section: Figurementioning

confidence: 99%

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Microbial Sterolomics as a Chemical Biology Tool

Haubrich

2018

Molecules

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Metabolomics has become a powerful tool in chemical biology. Profiling the human sterolome has resulted in the discovery of noncanonical sterols, including oxysterols and meiosis-activating sterols. They are important to immune responses and development, and have been reviewed extensively. The triterpenoid metabolite fusidic acid has developed clinical relevance, and many steroidal metabolites from microbial sources possess varying bioactivities. Beyond the prospect of pharmacognostical agents, the profiling of minor metabolites can provide insight into an organism’s biosynthesis and phylogeny, as well as inform drug discovery about infectious diseases. This review aims to highlight recent discoveries from detailed sterolomic profiling in microorganisms and their phylogenic and pharmacological implications.

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Recent update on antibacterial and antifungal activity of quinoline scaffolds

Dorababu¹

2020

Archiv der Pharmazie

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Although most of the heterocycles have been reported to possess a significant pharmacological activity, only a few of them, namely quinoline derivatives, have exhibited the finest biological activities. Despite the few medicinal properties of the plain quinoline molecule, its derivatives exhibit diverse pharmacological properties such as anticancer, anti‐inflammatory, antibacterial, antiviral, antifungal, antiprotozoal activities, and so on. The potential antimicrobial properties of the quinoline derivatives are evident from the decades of research on these derivatives. Owing to limitations like drug resistance, high cost, severe side effects, and less bioavailability of previously synthesized antimicrobial agents, these drugs have become obsolete in recent years. Hence, the design of more efficient antimicrobial drugs must be given topmost priority. A breakthrough in drug discovery is a must to prevent malevolent microbial diseases. Addressing all these issues, researchers have been continuously contributing to antimicrobial drug discovery. Herein, a short description of the pharmacology of antimicrobial agents such as antibacterials and antifungals synthesized recently is provided. The versatile derivatization of the quinoline moiety leading to significant antimicrobial potencies is discussed, considering the structure–activity relationship.

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Design, synthesis and evaluation of benzoheterocycle analogues as potent antifungal agents targeting CYP51

Cited by 26 publications

References 24 publications

Biological Evaluation, Qsar and Molecular Modeling Studies of 2,4-Dichlorobenzoic Acid Derivatives as Antimicrobial Agents

Biological Evaluation, Qsar and Molecular Modeling Studies of 2,4-Dichlorobenzoic Acid Derivatives as Antimicrobial Agents

Microbial Sterolomics as a Chemical Biology Tool

Recent update on antibacterial and antifungal activity of quinoline scaffolds

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