Design, synthesis and molecular docking and ADME studies of novel hydrazone derivatives for AChE inhibitory, BBB permeability and antioxidant effects DOI
Derya Osmani̇ye, Iqrar Ahmad, Begüm Nurpelin Sağlık

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2022, Volume and Issue: 41(18), P. 9022 - 9038

Published: Nov. 3, 2022

Alzheimer's disease (AD) is a progressive and fatal neurodegenerative that characterized by memory cognitive impairments predominantly affects the elderly most common cause of dementia. As known, AChE enzyme consists two parts. In this work, 10 new hydrazones (3a-3j) were designed synthesized. Naphthalene, indole, benzofuran benzothiophene rings used to interact with PAS region. 4-fluorophenyl 4-fluorobenzyl structures preferred for interaction CAS biological activity studies, BChE inhibitory potentials all compounds evaluated using in vitro Ellman method. The evaluation showed 3i 3j displayed significant against AChE. IC50 values 0.034 0.027 µM AChE, respectively. reference drug donepezil (IC50 = 0.021 µM) also inhibition addition, antioxidant activities evaluated. Derivatives 3j, which emerged active from both subjected PAMPA tests determine BBB permeability. Further docking simulation revealed these (3i, donepezil) interacted site similar manner donepezil. A few parameters derived MD trajectories computed validated protein-ligand complex's stability under dynamic conditions.Communicated Ramaswamy H. Sarma.

Language: Английский

Simulation-based approaches for drug delivery systems: Navigating advancements, opportunities, and challenges DOI Creative Commons

Iman Salahshoori,

Mahdi Golriz,

Marcos A.L. Nobre

et al.

Journal of Molecular Liquids, Journal Year: 2023, Volume and Issue: 395, P. 123888 - 123888

Published: Dec. 27, 2023

Efficient drug delivery systems (DDSs) play a pivotal role in ensuring pharmaceuticals' targeted and effective administration. However, the intricate interplay between formulations poses challenges their design optimization. Simulations have emerged as indispensable tools for comprehending these interactions enhancing DDS performance to address this complexity. This comprehensive review explores latest advancements simulation techniques provides detailed analysis. The encompasses various methodologies, including molecular dynamics (MD), Monte Carlo (MC), finite element analysis (FEA), computational fluid (CFD), density functional theory (DFT), machine learning (ML), dissipative particle (DPD). These are critically examined context of research. article presents illustrative case studies involving liposomal, polymer-based, nano-particulate, implantable DDSs, demonstrating influential simulations optimizing systems. Furthermore, addresses advantages limitations It also identifies future directions research development, such integrating multiple techniques, refining validating models greater accuracy, overcoming limitations, exploring applications personalized medicine innovative DDSs. employing like MD, MC, FEA, CFD, DFT, ML, DPD offer crucial insights into behaviour, aiding Despite advantages, rapid cost-effective screening, require validation addressing limitations. Future should focus on models, enhance outcomes. paper underscores contribution emphasizing providing valuable facilitating development optimization ultimately patient As we continue explore impact advancing discovery improving DDSs is expected be profound.

Language: Английский

Citations

52
Design, synthesis, in vitro anticancer and antimicrobial evaluation, SAR analysis, molecular docking and dynamic simulation of new pyrazoles, triazoles and pyridazines based isoxazole DOI
Hyam A. Radwan, Iqrar Ahmad, Ismail M. M. Othman

et al.

Journal of Molecular Structure, Journal Year: 2022, Volume and Issue: 1264, P. 133312 - 133312

Published: May 16, 2022

Language: Английский

Citations

55
Potent Bioactive Compounds From Seaweed Waste to Combat Cancer Through Bioinformatics Investigation DOI Creative Commons
Kaushik Kumar Bharadwaj, Iqrar Ahmad, Siddhartha Pati

et al.

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: April 22, 2022

The seaweed industries generate considerable amounts of waste that must be appropriately managed. This biomass from marine is a rich source high-value bioactive compounds. Thus, this can adequately utilized by recovering the compounds for therapeutic purposes. Histone deacetylases (HDACs) are key epigenetic regulators established as one most promising targets cancer chemotherapy. In present study, our objective to find HDAC 2 inhibitor. We performed top-down in silico methodologies identify potential inhibitors screening edible waste. One hundred ninety-three (n = 193) seaweeds were initially screened and filtered with drug-likeness properties using SwissADME. After that, followed further evaluate their binding protein Glide high throughput virtual (HTVS), standard precision (SP), extra (XP), quantum polarized ligand docking (QPLD). compound higher negative energy was selected, validate mode stability complex, molecular dynamics (MD) simulations Desmond performed. complex-binding free calculation mechanics-generalized born surface area (MM-GBSA) calculation. Post-MD simulation analyses such PCA, DCCM, landscape also evaluated. mechanical electronic assessed density functional theory (DFT) study. These findings support use resources like drug development its obtained results encourage vitro vivo research. Our show has affinity catalytic site properties, against cancer.

Language: Английский

Citations

53
Phytochemicals from Amberboa ramosa as potential DPP-IV inhibitors for the management of Type-II diabetes mellitus: Inferences from in-silico investigations DOI
Rakesh Kumar Paul, Iqrar Ahmad, Harun Patel

et al.

Journal of Molecular Structure, Journal Year: 2022, Volume and Issue: 1271, P. 134045 - 134045

Published: Aug. 30, 2022

Language: Английский

Citations

45
Synthesizes, characterization, molecular docking and in vitro bioactivity study of new compounds containing triple beta lactam rings DOI
Marwan Mohammed Farhan, Manaf A. Guma, Muwafaq Ayesh Rabeea

et al.

Journal of Molecular Structure, Journal Year: 2022, Volume and Issue: 1269, P. 133781 - 133781

Published: July 23, 2022

Language: Английский

Citations

39
Development of Isopropyl-Tailed Chalcones as a New Class of Selective MAO-B Inhibitors for the Treatment of Parkinson’s Disorder DOI Creative Commons
Sunil Kumar, Jong‐Min Oh, Mohamed A. Abdelgawad

et al.

ACS Omega, Journal Year: 2023, Volume and Issue: 8(7), P. 6908 - 6917

Published: Feb. 7, 2023

Thirteen isopropyl chalcones (CA1-CA13) were synthesized and evaluated for their inhibitory activity against monoamine oxidase (MAO). All compounds inhibited MAO-B more effectively than MAO-A. Compound CA4 most potently with an IC50 value of 0.032 μM, similar to that CA3 (IC50 = 0.035 μM) high selectivity index (SI) values over MAO-A (SI 49.75 353.23, respectively). The -OH (CA4) or -F (CA3) group at the para position on A ring provided higher inhibition other substituents (-OH ≥ > -Cl -Br -OCH2CH3 -CF3). On hand, compound CA10 0.310 μM 0.074 μM). Br-containing thiophene substituent (CA10) instead showed highest inhibition. In a kinetic study, Ki 0.076 ± 0.001 0.027 0.002 respectively, was 0.016 0.005 μM. reversibility study reversible inhibitors inhibitor docking molecular dynamics, hydroxyl two hydrogen bonds contributed stability protein-ligand complex. These results suggest are potent selective can be used treatment Parkinson's disease.

Language: Английский

Citations

29
Design and synthesis of some novel hybrid molecules based on 4-thiazolidinone bearing pyridine-pyrazole scaffolds: molecular docking and molecular dynamics simulations of its major constituent onto DNA gyrase inhibition DOI
Nisheeth C. Desai, Dharmpalsinh J. Jadeja, Aratiba M. Jethawa

et al.

Molecular Diversity, Journal Year: 2023, Volume and Issue: 28(2), P. 693 - 709

Published: Feb. 8, 2023

Language: Английский

Citations

23
Unraveling the crystal structure, stability and drug likeness of 1,3,4-oxadiazole derivatives against Myelofibrosis: a combined experimental and computational investigation DOI
T.N. Lohith, Chikkappaiahnayaka Santhosh, Mofeli Benedict Leoma

et al.

Journal of Biomolecular Structure and Dynamics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 15

Published: March 31, 2024

Herein, we report the synthesis and characterization of novel 1,3,4-oxadiazole derivatives, 2-methoxybenzyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate (C1) 5-(2-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate (C2), methoxybenzyl 5-(3-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate (C3) obtained through desulfurative cyclization reaction. The compound C2 was crystallized, its crystal structure elucidated using single-crystal X-ray diffraction technique. Hirshfeld surface analysis carried out to analyze, visualize globally appreciate weak interactions involved in packing. These analyses were complemented by Quantum Theory Atoms In Molecules (QTAIM) Reduced Density Gradient (RDG), which allowed us decipher nature types attractive forces that contribute maintain titled compound. Moreover, ADME profile predicted assess drug likeness. Finally, silico studies performed explore binding affinity compounds (C1–3) against Myelofibrosis molecular docking dynamic simulations.

Language: Английский

Citations

11
Aromatase Inhibitors as a Promising Direction for the Search for New Anticancer Drugs DOI Creative Commons
Sara Janowska, Serhii Holota, Roman Lesyk

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(2), P. 346 - 346

Published: Jan. 10, 2024

Aromatase is an enzyme that plays a crucial role in the biosynthesis of estrogens, which are hormones contribute to growth certain types breast cancer. In particular, aromatase catalyzes conversion androgens (male hormones) into estrogens (female various tissues, including adrenal glands, ovaries, and adipose tissue. Given estrogen promoting hormone-receptor-positive cancers, has become important molecular target for development anticancer agents. inhibitors can be classified two main groups based on their chemical structure: steroidal non-steroidal inhibitors. This work presents review literature from last ten years regarding search new We present directions search, taking account impact structure modifications activity.

Language: Английский

Citations

8
Isolation, characterization, and multimodal evaluation of novel glycolipid biosurfactant derived from Bacillus species: A promising Staphylococcus aureus tyrosyl-tRNA synthetase inhibitor through molecular docking and MD simulations DOI
Rohit Das, Subhadarsini Sahoo, Sudhir Kumar Paidesetty

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 261, P. 129848 - 129848

Published: Feb. 1, 2024

Language: Английский

Citations

8