Synthesis, Molecular Docking Studies and Antifungal Activity Evaluation of New Thiazolyl-methylen-1,3,4-oxadiazolines as Potential Lanosterol 14a-demethylase Inhibitors

Considering the well-established antifungal activity of azole compounds, a new series of thiazolyl-methylen-1,3,4-oxadiazolines derivatives were designed and synthesized as lanosterol-demethylase inhibitors. The final compounds were screened for antifungal activity against the Candida albicans ATCC 90028 strain. Molecular docking studies were performed to investigate the interaction modes between the compounds and the active site of lanosterol 14a-demethylase, which is a target enzyme for anticandidal azoles. Theoretical ADME predictions were also calculated for the final compounds 5a-h. Keywords: Thiazolyl-methylen-1,3,4-oxadiazolines, Candida albicans, lanosterol 14a-demethylase

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Synthesis of New Bis-pyrazolines Endowed with Potent Antifungal Activity against Candida albicans and Aspergillus niger

Letters in Drug Design & Discovery ◽

10.2174/1570180817999201008155247 ◽

2020 ◽

Vol 17 ◽

Author(s):

Belgin Sever ◽

Mehlika Dilek Altıntop ◽

Ahmet Özdemir

Keyword(s):

Candida Albicans ◽

Molecular Docking ◽

Antifungal Activity ◽

Aspergillus Niger ◽

Mtt Assay ◽

Active Site ◽

Antifungal Agents ◽

Docking Studies ◽

Antifungal Effects ◽

Nih 3T3

Background: Due to the increasing number of cases of invasive fungal infections (IFIs), there is an urgent need to identify potent antifungal agents capable of combating IFIs. Pyrazolines are one such class of therapeutically active agents that could be considered to fulfil this need. Objective: In this context, this paper aims to identify two new series of bis-pyrazolines endowed with potent antifungal activity against Candida albicans and Aspergillus niger. Methods: Two new series of bis-pyrazolines (4a-i, 5a-e) were synthesized through an efficient and and versatile synthetic procedure. The compounds were screened for their antifungal effects on C. albicans and A. niger using a broth microdilution method. Their cytotoxic effects on NIH/3T3 mouse embryonic fibroblast cell line were determined using MTT assay. Molecular docking studies were performed in the active site of lanosterol 14α-demethylase (CYP51) to shed light on their antifungal effects using Schrödinger’s Maestro molecular modeling package. Results And Discussion: 5,5'-(1,4-Phenylene)bis[1-(2-(5-phenyl-1,3,4-oxadiazol-2-yl)thio)acetyl)-3-(2-thienyl)-4,5- dihydro-1H-pyrazole] (4a) and 5,5'-(1,4-phenylene)bis[1-(2-(4-(2-hydroxyethyl)-1-piperazinylthiocarbamoyl)thio)acetyl)-3- (2-thienyl)-4,5-dihydro-1H-pyrazole] (5a) were found as the most promising antifungal agents in this series. Compounds 4a and 5a showed pronounced antifungal activity against C. albicans (MIC= 0.016 mg/mL) and A. niger (MIC= 0.008 mg/mL). Based on MTT assay, their antifungal effects were selective (IC50 > 0.500 mg/mL for NIH/3T3 cell line). Molecular docking studies suggested that compounds 5a-e might show their anticandidal effects via CYP51 inhibition in regard to their stronger interactions in the active site of CYP51. Conclusion: Compounds 4a and 5a stand out as potential antifungal agents for the management of IFIs caused by C. albicans and A. niger.

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Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol 14α-Demethylase Inhibitors

Journal of Chemistry ◽

10.1155/2017/9387102 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 10

Author(s):

Nafiz Öncü Can ◽

Ulviye Acar Çevik ◽

Begüm Nurpelin Sağlık ◽

Serkan Levent ◽

Büşra Korkut ◽

...

Keyword(s):

Molecular Docking ◽

Antifungal Activity ◽

Active Site ◽

Candida Parapsilosis ◽

Docking Studies ◽

Candida Krusei ◽

Ergosterol Biosynthesis ◽

Molecular Docking Studies ◽

Chemical Structures ◽

Nih 3T3

Due to anticandidal importance of azole compounds, a new series of benzimidazole-triazole derivatives(5a–5s)were designed and synthesized as ergosterol inhibitors. The chemical structures of the target compounds were characterized by spectroscopic methods. The final compounds were screened for antifungal activity againstCandida glabrata(ATCC 90030),Candida krusei(ATCC 6258),Candida parapsilosis(ATCC 22019), andCandida albicans(ATCC 24433). Compounds5iand5sexhibited significant inhibitory activity againstCandidastrains with MIC50values ranging from 0.78 to 1.56 μg/mL. Cytotoxicity results revealed that IC50values of compounds5iand5sagainst NIH/3T3 are significantly higher than their MIC50values. Effect of the compounds5iand5sagainst ergosterol biosynthesis was determined by LC-MS-MS analysis. Both compounds caused a significant decrease in the ergosterol level. The molecular docking studies were performed to investigate the interaction modes between the compounds and active site of lanosterol 14-α-demethylase (CYP51), which is as a target enzyme for anticandidal azoles. Theoretical ADME predictions were also calculated for final compounds.

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5-Benzyliden-2-(5-Methylthiazol-2-Ylimino)Thiazolidin-4-Ones as Antimicrobial Agents. Design, Synthesis, Biological Evaluation and Molecular Docking Studies

Antibiotics ◽

10.3390/antibiotics10030309 ◽

2021 ◽

Vol 10 (3) ◽

pp. 309

Author(s):

Michelyne Haroun ◽

Christophe Tratrat ◽

Aggeliki Kolokotroni ◽

Anthi Petrou ◽

Athina Geronikaki ◽

...

Keyword(s):

Molecular Docking ◽

Antifungal Activity ◽

Antimicrobial Agents ◽

Docking Studies ◽

Biological Evaluation ◽

Design Synthesis ◽

Molecular Docking Studies ◽

E Coli ◽

Antibacterial And Antifungal Activities ◽

Lanosterol Demethylase

In this study, we report the design, synthesis, computational and experimental evaluation of the antimicrobial activity, as well as docking studies of new 5-methylthiazole based thiazolidinones. All compounds demonstrated antibacterial efficacy, some of which (1,4,10 and 13) exhibited good activity against E. coli and B. cereus. The evaluation of antibacterial activity against three resistant strains, MRSA, P. aeruginosa and E. coli, revealed that compound 12 showed the best activity, higher than reference drugs ampicillin and streptomycin, which were inactive or exhibited only bacteriostatic activity against MRSA, respectively. Ten out of fifteen compounds demonstrated higher potency than reference drugs against a resistant strain of E. coli, which appeared to be the most sensitive species to our compounds. Compounds 8, 13 and 14 applied in a concentration equal to MIC reduced P. aeruginosa biofilm formation by more than 50%. All compounds displayed antifungal activity, with compound 10 being the most active. The majority of compounds showed better activity than ketoconazole against almost all fungal strains. In order to elucidate the mechanism of antibacterial and antifungal activities, molecular docking studies on E. coli Mur B and C. albicans CYP51 and dihydrofolate reductase were performed. Docking analysis of E. coli MurB indicated a probable involvement of MurB inhibition in the antibacterial mechanism of tested compounds while docking to 14α-lanosterol demethylase (CYP51) and tetrahydrofolate reductase of Candida albicans suggested that probable involvement of inhibition of CYP51 reductase in the antifungal activity of the compounds. Potential toxicity toward human cells is also reported.

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Bis coumarinyl bis triazolothiadiazinyl ethane derivatives: Synthesis, antiviral activity evaluation, and molecular docking studies

Synthetic Communications ◽

10.1080/00397911.2018.1455871 ◽

2018 ◽

Vol 48 (12) ◽

pp. 1494-1503 ◽

Cited By ~ 4

Author(s):

Sreenu Pavurala ◽

Krishnaiah Vaarla ◽

Rajeshkumar Kesharwani ◽

Lieve Naesens ◽

Sandra Liekens ◽

...

Keyword(s):

Molecular Docking ◽

Antiviral Activity ◽

Docking Studies ◽

Molecular Docking Studies ◽

Activity Evaluation

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Synthesis, characterization and molecular docking studies on some new N-substituted 2-phenylpyrido[2,3-d]pyrimidine derivatives

Research Journal of Pharmacy and Technology ◽

10.52711/0974-360x.2021.00667 ◽

2021 ◽

pp. 3846-3854

Author(s):

Vivek B. Panchabhai ◽

Santosh R. Butle ◽

Parag G. Ingole

Keyword(s):

Crystal Structure ◽

Antibacterial Activity ◽

Molecular Docking ◽

Active Site ◽

Docking Studies ◽

Biotin Carboxylase ◽

Active Site Residues ◽

Pyrimidine Derivatives ◽

Molecular Docking Studies ◽

Novel Scaffold

We report a novel scaffold of N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives with potent antibacterial activity by targeting this biotin carboxylase enzyme. The series of eighteen N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives were synthesized, characterized and further molecular docking studied to determine the mode of binding and energy changes with the crystal structure of biotin carboxylase (PDB ID: 2V58) was employed as the receptor with compounds 6a-r as ligands. The results obtained from the simulation were obtained in the form of dock score; these values represent the minimum energies. Compounds 6d, 6l, 6n, 6o, 6r and 6i showed formation of hydrogen bonds with the active site residues and van Der Walls interactions with the biotin carboxylase enzyme in their molecular docking studies. This compound can be studied further and developed into a potential antibacterial lead molecule.

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Pyrazolobenzothiazine-based carbothioamides as new structural leads for the inhibition of monoamine oxidases: design, synthesis, in vitro bioevaluation and molecular docking studies

MedChemComm ◽

10.1039/c6md00570e ◽

2017 ◽

Vol 8 (2) ◽

pp. 452-464 ◽

Cited By ~ 10

Author(s):

Syed Mobasher Ali Abid ◽

Sana Aslam ◽

Sumera Zaib ◽

Syeda Mahwish Bakht ◽

Matloob Ahmad ◽

...

Keyword(s):

Molecular Docking ◽

Active Site ◽

Potent Inhibitor ◽

Binding Mode ◽

Docking Studies ◽

Design Synthesis ◽

Molecular Docking Studies ◽

Monoamine Oxidases ◽

Mao B

Binding mode of potent inhibitor (green) & cognate ligand (pink) in the active site of MAO-B.

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Synthesis, characterization, and bio-activity evaluation of thiourea derivatives of epinephrine as antimicrobial and antioxidant agents: molecular docking studies

Monatshefte für Chemie - Chemical Monthly ◽

10.1007/s00706-017-1938-4 ◽

2017 ◽

Vol 148 (8) ◽

pp. 1525-1537 ◽

Cited By ~ 6

Author(s):

H. Sudhamani ◽

S. K. Thaslim Basha ◽

S. Adam ◽

B. Vijay Bhaskar ◽

C. Naga Raju

Keyword(s):

Molecular Docking ◽

Docking Studies ◽

Thiourea Derivatives ◽

Molecular Docking Studies ◽

Activity Evaluation ◽

Antioxidant Agents ◽

Derivatives Of

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Synthesis and Molecular Docking of New Thiophene Derivatives as Lactate Dehydrogenase-A Inhibitors

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557519666190212165302 ◽

2019 ◽

Vol 19 (10) ◽

pp. 833-841 ◽

Cited By ~ 1

Author(s):

Abd El-Galil E. Amr ◽

Mohamed F. El-Shehry ◽

Alhussein A. Ibrahim ◽

Hanaa M. Hosni ◽

Mohamed A. Al-Omar ◽

...

Keyword(s):

Molecular Docking ◽

Lactate Dehydrogenase ◽

Glucose Metabolism ◽

Cancer Cells ◽

Active Site ◽

Docking Studies ◽

Reference Drug ◽

Molecular Docking Studies ◽

Thiophene Moiety ◽

Thiophene Derivatives

Background & Objective: A series of novel derivatives possessing the thiophene moiety were synthesized using ethyl 5'-amino-2,3'-bithiophene-4'-carboxylate as the starting material. Methods: The new synthesized derivatives were screened as lactate dehydrogenase (LDH) inhibitors. LDH plays an important role in glucose metabolism in cancer cells and can affect tumor genesis and metastasis. Results: 3-Substituted p-tolylthieno[2,3-d]pyrimidin-4(3H)-ones 4 were the most potent inhibitors in this study compared to Galloflavin reference drug. Conclusion: Molecular docking studies on the Human Lactate Dehydrogenase active site were carried out on the synthesized compounds and the MolDock scores ranged between -127 to -171.

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