scholarly journals Studies in molecular modeling, in-vitro CDK2 inhibition and antimetastatic activity of some synthetic flavones

10.2741/4911 ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 664-681
Author(s):  
Ojas,S Wagal
Keyword(s):  
Molecular Modeling ◽  
Antimetastatic Activity

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

2020 ◽  
Vol 17 (2) ◽  
pp. 169-183 ◽  
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.

scholarly journals Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1838
Author(s):  
Naglaa M. Ahmed ◽  
Mahmoud M. Youns ◽  
Moustafa K. Soltan ◽  
Ahmed M. Said
Keyword(s):  
Molecular Modeling ◽  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

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

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

Development of Natural Bioactive Alkaloids: Anticancer perspective

2021 ◽  
Vol 21 ◽  
Author(s):  
Ashish Patel ◽  
Ravi Vanecha ◽  
Jay Patel ◽  
Divy Patel ◽  
Umang Shah ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Low Cost ◽  
Chemical Compounds ◽  
Cost Effective ◽  
Drug Discovery And Development ◽  
Anticancer Properties ◽  
Antimetastatic Activity ◽  
New Chemical Entities

: Cancer is a frightful disease that still poses a 'nightmare' worldwide, causing millions of casualties annually due to one of the human race's most significant healthcare challenges that requires a pragmatic treatment strategy. However, plants and plant-derived products revolutionize the field as they are quick, cleaner, eco-friendly, low-cost, effective, and less toxic than conventional treatment methods. Plants are repositories for new chemical entities and have a promising cancer research path, supplying 60% of the anticancer agents currently used. Alkaloids are important chemical compounds that serve as a rich reservoir for drug discovery and development. However, some alkaloids derived from natural herbs display anti-proliferation and antimetastatic activity on different forms of cancer, both in vitro and in vivo. Alkaloids have also been widely formulated as anticancer medications, such as camptothecin and vinblastine. Still, more research and clinical trials are required before final recommendations can be made on specific alkaloids. This review focuses on the naturally-derived bioactive alkaloids with prospective anticancer properties based on the information in the literature.

scholarly journals 2-Position Base-Modified Analogues of Adenophostin A as High-Affinity Agonists of thed-myo-Inositol Trisphosphate Receptor:  In Vitro Evaluation and Molecular Modeling

2008 ◽  
Vol 73 (5) ◽  
pp. 1682-1692 ◽  
Author(s):  
Kana M. Sureshan ◽  
Melanie Trusselle ◽  
Stephen C. Tovey ◽  
Colin W. Taylor ◽  
Barry V. L. Potter
Keyword(s):  
Molecular Modeling ◽  
Inositol Trisphosphate ◽  
In Vitro Evaluation ◽  
Inositol Trisphosphate Receptor ◽  
High Affinity ◽  
Adenophostin A ◽  
Trisphosphate Receptor

A new class of serotonin 5‐HT 2A /5‐HT 2C receptor inverse agonists: Synthesis, molecular modeling, in vitro and in vivo pharmacology of novel 2‐aminotetralins

2021 ◽  
Author(s):  
Austen B. Casey ◽  
Munmun Mukherjee ◽  
Ryan P. McGlynn ◽  
Meng Cui ◽  
Stephen J. Kohut ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Inverse Agonists ◽  
New Class

scholarly journals BIOLOGICAL EVALUATION, QSAR AND MOLECULAR MODELING STUDIES OF 2,4-DICHLOROBENZOIC ACID DERIVATIVES AS ANTIMICROBIAL AGENTS

2019 ◽  
pp. 98-105
Author(s):  
SAMRIDHI THAKRAL ◽  
VIKRAMJEET SINGH
Keyword(s):  
Molecular Modeling ◽  
Antimicrobial Agents ◽  
Structural Characteristics ◽  
Docking Simulation ◽  
Biological Evaluation ◽  
Dilution Method ◽  
Bacterial Strains ◽  
Qsar Studies ◽  
Antimicrobial Potential

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.

scholarly journals Molecular Modeling of µ Opioid Receptor Ligands with Various Functional Properties: PZM21, SR-17018, Morphine, and Fentanyl—Simulated Interaction Patterns Confronted with Experimental Data

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4636 ◽  
Author(s):  
Sabina Podlewska ◽  
Ryszard Bugno ◽  
Lucja Kudla ◽  
Andrzej J. Bojarski ◽  
Ryszard Przewlocki
Keyword(s):  
Molecular Modeling ◽  
G Protein ◽  
Opioid Receptor ◽  
Pearson Correlation ◽  
Interaction Patterns ◽  
Receptor Ligands ◽  
Opioid Receptor Ligands ◽  
Dynamics Simulations

Molecular modeling approaches are an indispensable part of the drug design process. They not only support the process of searching for new ligands of a given receptor, but they also play an important role in explaining particular activity pathways of a compound. In this study, a comprehensive molecular modeling protocol was developed to explain the observed activity profiles of selected µ opioid receptor agents: two G protein-biased µ opioid receptor agonists (PZM21 and SR-17018), unbiased morphine, and the β-arrestin-2-biased agonist, fentanyl. The study involved docking and molecular dynamics simulations carried out for three crystal structures of the target at a microsecond scale, followed by the statistical analysis of ligand–protein contacts. The interaction frequency between the modeled compounds and the subsequent residues of a protein during the simulation was also correlated with the output of in vitro and in vivo tests, resulting in the set of amino acids with the highest Pearson correlation coefficient values. Such indicated positions may serve as a guide for designing new G protein-biased ligands of the µ opioid receptor.

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