In Silico Study, Physicochemical, and In Vitro Lipase Inhibitory Activity of α,β-Amyrenone Inclusion Complexes with Cyclodextrins

α,β-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with γ- and β-cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties. Molecular modeling studies indicated that the CD:ABAME ICs prepared at a 2:1 molar ratio would be more stable to the complexation process than those prepared at a 1:1 molar ratio. The physicochemical characterization showed strong evidence that corroborates with the in silico results, and the formation of ICs with CD was capable of inducing changes in ABAME physicochemical properties. ICs was shown to be a stronger inhibitor of lipase activity than Orlistat and to potentiate the inhibitory effects of ABAME on porcine pancreatic enzymes. In conclusion, a new pharmaceutical preparation with potentially improved physicochemical characteristics and inhibitory activity toward lipases was developed in this study, which could prove to be a promising ingredient for future formulations.

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Syntheses of new 3-thiazolyl coumarin derivatives, in vitro α -glucosidase inhibitory activity, and molecular modeling studies

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2016.06.037 ◽

2016 ◽

Vol 122 ◽

pp. 196-204 ◽

Cited By ~ 41

Author(s):

Uzma Salar ◽

Muhammad Taha ◽

Khalid Mohammed Khan ◽

Nor Hadiani Ismail ◽

Syahrul Imran ◽

...

Keyword(s):

Molecular Modeling ◽

Inhibitory Activity ◽

Coumarin Derivatives ◽

Modeling Studies ◽

Molecular Modeling Studies

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p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180816666181128112249 ◽

2020 ◽

Vol 17 (2) ◽

pp. 169-183 ◽

Cited By ~ 1

Author(s):

İrem Bozbey ◽

Suat Sari ◽

Emine Şalva ◽

Didem Kart ◽

Arzu Karakurt

Keyword(s):

Molecular Modeling ◽

Neuroblastoma Cell ◽

Neuroblastoma Cells ◽

Cytotoxic Agents ◽

Human Neuroblastoma Cell ◽

Human Neuroblastoma ◽

Modeling Studies ◽

Broth Microdilution Method ◽

Molecular Modeling Studies

Background: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immunecompromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 µM. In this line, 3 was the most potent with an IC50 value of 82.18 μM followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.

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Novel benzenesulfonamides aryl and arylsulfone conjugates adopting tail/dual tail approaches: Synthesis, carbonic anhydrase inhibitory activity and molecular modeling studies

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2021.113486 ◽

2021 ◽

pp. 113486

Author(s):

Assem H. Eldeeb ◽

Mahmoud F. Abo-Ashour ◽

Andrea Angeli ◽

Alessandro Bonardi ◽

Deena S. Lasheen ◽

...

Keyword(s):

Molecular Modeling ◽

Carbonic Anhydrase ◽

Inhibitory Activity ◽

Modeling Studies ◽

Molecular Modeling Studies

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New quinoxalin‐1,3,4‐oxadiazole derivatives: Synthesis, characterization, in vitro biological evaluations, and molecular modeling studies

Archiv der Pharmazie ◽

10.1002/ardp.202000471 ◽

2021 ◽

Author(s):

Roghieh Mirzazadeh ◽

Mohammad S. Asgari ◽

Ebrahim Barzegari ◽

Keyvan Pedrood ◽

Maryam Mohammadi‐Khanaposhtani ◽

...

Keyword(s):

Molecular Modeling ◽

Modeling Studies ◽

Oxadiazole Derivatives ◽

Molecular Modeling Studies

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Molecular Modeling Studies on 2,4-Disubstituted Imidazopyridines as Anti-Malarials: Atom-Based 3D-QSAR, Molecular Docking, Virtual Screening, In-Silico ADMET and Theoretical Analysis

Journal of Computational Biophysics and Chemistry ◽

10.1142/s2737416521500125 ◽

2021 ◽

pp. 2150012

Author(s):

Suraj N. Mali ◽

Anima Pandey

Keyword(s):

Molecular Docking ◽

Molecular Modeling ◽

Virtual Screening ◽

In Silico ◽

Energy Gap ◽

3D Qsar ◽

Modeling Studies ◽

In Vitro Investigation ◽

In Silico Admet ◽

Molecular Modeling Studies

Malarial parasites have been reported for moderate-high resistance towards classical antimalarial agents and henceforth development of newer novel chemical entities targeting multiple targets rather than targeting single target will be a highly promising strategy in antimalarial drug discovery. Herein, we carried out molecular modeling studies on 2,4-disubstituted imidazopyridines as anti-hemozoin formation inhibitors by using Schrödinger’s molecular modeling package (2020_4). We have developed statistically robust atom-based 3D-QSAR model (training set, [Formula: see text]; test set, [Formula: see text]; [Formula: see text] [Formula: see text]; root-mean-square error, [Formula: see text]; standard deviation, [Formula: see text]). Our molecular docking, in-silico ADMET analysis showed that dataset molecule 37, has highly promising results. Our ligand-based virtual screening resulted in top five ZINC hits, among them ZINC73737443 hit was observed with lesser energy gap, i.e. 7.85[Formula: see text]eV, higher softness value (0.127[Formula: see text]eV), and comparatively good docking score of [Formula: see text]10.2[Formula: see text]kcal/mol. Our in-silico analysis for a proposed hit, ZINC73737443 showed that this molecule has good ADMET, in-silico nonames toxic as well as noncarcinogenic profile. We believe that further experimental as well as the in-vitro investigation will throw more lights on the identification of ZINC73737443 as a potential antimalarial agent.

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