Attaching azoles to Hantzsch 1,4-dihydropyridines: Synthesis, theoretical investigation of nonlinear optical properties, antimicrobial evaluation and molecular docking studies

Gündüz, Miyase Gözde; Dengiz, Çağatay; Aslan, Ebru Koçak; Nikodinović‐Runić, Jasmina

doi:10.1016/j.molstruc.2021.131316

Cited by 9 publications

(5 citation statements)

References 45 publications

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“…In the beginning, we examined how fluconazole interacts with CYP51 upon binding. Fluconazole forms the axial coordination with the iron of the heme cofactor through N‐4 of its triazole ring and π‐π stacking with the heme, which is characteristic for azole antifungals [45] . The synthesized compounds 16 – 21 lack this kind of interaction with the heme iron and bind with the active site residues at the substrate entry channel only, which is the most important reason for their low efficacy.…”

Section: Resultsmentioning

confidence: 99%

“…Fluconazole forms the axial coordination with the iron of the heme cofactor through N-4 of its triazole ring and π-π stacking with the heme, which is characteristic for azole antifungals. [45] The synthesized compounds 16-21 lack this kind of interaction with the heme iron and bind with the active site residues at the substrate entry channel only, which is the most important reason for their low efficacy. However, this heme-azole connection can also cause side effects by binding to host lanosterol-14α-demethylase or non-targeted cytochrome P450 enzymes important for drug metabolism and reproduction.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

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Synthesis, Anti‐Fungal Potency and In silico Studies of Novel Steroidal 1,4‐Dihydropyridines

Khan

Iqbal

Ahmedi

et al. 2023

Chemistry & Biodiversity

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Working principle of azoles as antifungals is the inhibition of fungal CYP51/lanosterol‐14α‐demethylase via selective coordination with heme iron. This interaction can also cause side effects by binding to host lanosterol‐14α‐demethylase. Hence, it is necessary to design, synthesize and test new antifungal agents that have different structures than those of azoles and other antifungal drugs of choice in clinical practice. Consequently, a series of steroidal 1,4‐dihydropyridine analogs 16–21 were synthesized and screened for their in vitro anti‐fungal activity against three Candida species as steroids‐based medications have low toxicity, less vulnerability to multi‐drug resistance, and high bioavailability by being capable of penetrating the cell wall and binding to specific receptors. Initially, Claisen–Schmidt condensation takes place between steroidal ketone (dehydroepiandrosterone) and an aromatic aldehyde forming steroidal benzylidene 8–13 followed by Hantzsch 1,4‐dihydropyridine synthesis resulting in steroidal 1,4‐dihydropyridine derivatives 16–21. The results exhibited that compound 17 has significant anti‐fungal potential with an MIC value of 750 μg/ml for C. albicans and C. glabrata and 800 μg/ml for C. tropicalis. In silico molecular docking and ADMET studies were also performed for compounds 16–21.

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Section: Resultsmentioning

confidence: 99%

Section: Molecular Docking Studiesmentioning

confidence: 99%

Synthesis, Anti‐Fungal Potency and In silico Studies of Novel Steroidal 1,4‐Dihydropyridines

Khan

Iqbal

Ahmedi

et al. 2023

Chemistry & Biodiversity

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“…The fungi were tested on a base medium called potato Dextrose agar (PDA). The further procedure followed the method cited in [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

“…Besides synthesis and biological experiments, computational studies are becoming the crucial tool in organic research focusing on structure orientation, compound behavior, molecular properties prediction, ligand–protein interactions, binding energies, and others [ 21 ]. In recent years, numerous results related to machine-assisted studies combined with synthetic research have been published [ 22 , 23 , 24 , 25 , 26 ]. As far as we are aware, there are currently no reports combining information about DHP, its environmentally friendly manufacturing method, biological properties, and computer simulations.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic and Infection-Controlled Investigations of Novel Dihydropyridine Hybrids: An Efficient Synthesis and Molecular-Docking Studies

et al. 2023

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A sequence of novel 1,4-dihydropyridines (DHP) and their hybrids was developed using a multicomponent strategy under environmentally benign conditions. In addition, computational studies were performed, and the ligand–protein interactions calculated in different bacteria and two fungal strains. Para-hydroxy-linked DHP (5f) showed the best binding energies of 3.591, 3.916, 8.499 and 6.895 kcal/mol against various pathogens used and other substances received a good docking score. The pathogen resistance potential of the synthesized targets against four bacteria and two fungi showed that whole DHP substances exhibit different levels of resistance to each microorganism. Gram-positive bacteria, which are highly sensitive to all molecules, and the MTCC-1884-encoded fungus strongly rejected the studied compounds compared to comparator drugs. In particular, the 5f candidate showed remarkable antimicrobial activity, followed by the substances 5a, 5b, 5j, 5k and 5l. Furthermore, MIC and MBC/MFC properties showed that 5f had a minimum bacterial concentration of 12.5 μg/mL against E. coli and against two fungal pathogens, with its killing activity being effective even at low concentrations. On the other hand, whole motifs were tested for their cytotoxic activity, revealing that the methoxy and hydroxy-linked compounds (5h) showed greater cytotoxic potency, followed by the two hydroxy linked compounds (5d and 5f). Overall, this synthetic approach used represents a prototype for future nature-favored synthesis methods and these biological results serve as a guide for future therapeutic drug research. However, the computer results play an important role in the further development of biological experiments.

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“…These modulations at the C3-and C5-positions alter tissue selectivity. [11][12][13] The new therapeutic utility of 1,4-dihydropyridine derivatives is a breakthrough in current clinical trials, encompassing their antimicrobial, 14,15 anticoagulant, 16 antihypertensive, 17 analgesic, 18,19 anticancer, 20 cytotoxic, 21 antitumor activities. 22,23 For instance, we previously reported the anticoagulant and antimicrobial activities of 1,4-dihydropyridine derivatives 24 and other pharmaceutical activities such as analgesic 25,26 and anti-inflammatory.…”

Section: Introductionmentioning

confidence: 99%

Design of 1,4-Dihydropyridine Hybrid Benzamide Derivatives: Synthesis and Evaluation of Analgesic Activity and Their Molecular Docking Studies

Idhayadhulla¹,

Surendrakumar²,

Meenakshisundaram³

et al. 2022

DDDT

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This study aims to determine the analgesic activity of 1,4-dihydropyridine hybrid benzamide derivatives. These hybrid derivatives were synthesized, and their analgesic activity was studied. The synthesis method applied was a one-step reaction involving a green chemistry approach. Methods: The compounds were prepared via the amination method with a yield ranging between 82% and 93%. The title compounds were confirmed by means of IR, 1 H and 13 C NMR, and mass spectral analyses. The pharmacological activity of all the synthesized compounds was evaluated, and the analgesic activities were monitored in vivo (by tail immersion methods), with a digital analgesiometer. The drug response and damage of tail ata concentration of 10 mg/kg were measured by tail-flicking latency. Results: The activity of compound 2c (81.35% activity at 5mg/kg) can be correlated with its salicylamidemoiety (13.99% activity at 5mg/kg), and diclofenac showed comparable activity (79.21% activity at 5mg/kg reference drugs). Compound 2c has a higher potential to inhibit COX proteins compared to diclofenac. The drug-like nature of the molecule 2c corresponds to its ADME properties. Conclusion:In this study, all the synthesized compounds were found to possess significant analgesic activities; particularly, the performance of compound 2c is excellent. Thus, the preparative method described is an apt route for developing novel therapeutic formulations.

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Attaching azoles to Hantzsch 1,4-dihydropyridines: Synthesis, theoretical investigation of nonlinear optical properties, antimicrobial evaluation and molecular docking studies

Cited by 9 publications

References 45 publications

Synthesis, Anti‐Fungal Potency and In silico Studies of Novel Steroidal 1,4‐Dihydropyridines

Synthesis, Anti‐Fungal Potency and In silico Studies of Novel Steroidal 1,4‐Dihydropyridines

Cytotoxic and Infection-Controlled Investigations of Novel Dihydropyridine Hybrids: An Efficient Synthesis and Molecular-Docking Studies

Design of 1,4-Dihydropyridine Hybrid Benzamide Derivatives: Synthesis and Evaluation of Analgesic Activity and Their Molecular Docking Studies

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