MyMedR

Displaying all 5 publications

Abstract:

Sort:

Synthesis, anti-acetylcholinesterase evaluation, molecular docking and molecular dynamics simulation of novel Psoralen derivatives

Hasan AH, Mohamed Yusof FS, Kamarudin NA, Murugesan S, Shakya S, Jamalis J

Curr Org Synth, 2023 Mar 28.
PMID: 36998126 DOI: 10.2174/1570179420666230328121554

INTRODUCTION: Seven new psoralen derivatives were synthesised by carbodiimide coupling to active carboxylic acid to amide formation in mild reaction conditions.
METHODS: The psoralen derivatives were produced through the condensation of seven different types of amine groups consisting of electron withdrawing groups and electron donating groups.
RESULTS: All the synthesised compounds were obtained with moderate to high yields. Structural characterization using ATR-FTIR, 1H NMR, 13C NMR, and HRMS has confirmed their structure. Moreover, in silico evaluation of the psoralen derivatives against the AChE enzyme was performed, and acetylcholinesterase inhibitory activity of psoralen derivatives was also conducted.
CONCLUSION: Results from molecular docking show the potential of compound 12e as AChE inhibitors due to its highest binding energy value. It was further supported by the anti-acetylcholinesterase activity of compound 12e, which has 91.69% inhibition, comparable to galantamine (94.12%). Furthermore, 100 ns run molecular dynamics (MD) simulation was used to refine docking results.
Fulltext Potential inhibitory activity of phytoconstituents against black fungus: In silico ADMET, molecular docking and MD simulation studies

Hamaamin Hussen N, Hameed Hasan A, Jamalis J, Shakya S, Chander S, Kharkwal H, et al.

Comput Toxicol, 2022 Nov;24:100247.
PMID: 36193218 DOI: 10.1016/j.comtox.2022.100247

Mucormycosis or "black fungus" has been currently observed in India, as a secondary infection in COVID-19 infected patients in the post-COVID-stage. Fungus is an uncommon opportunistic infection that affects people who have a weak immune system. In this study, 158 antifungal phytochemicals were screened using molecular docking against glucoamylase enzyme of Rhizopus oryzae to identify potential inhibitors. The docking scores of the selected phytochemicals were compared with Isomaltotriose as a positive control. Most of the compounds showed lower binding energy values than Isomaltotriose (-6.4 kcal/mol). Computational studies also revealed the strongest binding affinity of the screened phytochemicals was Dioscin (-9.4 kcal/mol). Furthermore, the binding interactions of the top ten potential phytochemicals were elucidated and further analyzed. In-silico ADME and toxicity prediction were also evaluated using SwissADME and admetSAR online servers. Compounds Piscisoflavone C, 8-O-methylaverufin and Punicalagin exhibited positive results with the Lipinski filter and drug-likeness and showed mild to moderate of toxicity. Molecular dynamics (MD) simulation (at 300 K for 100 ns) was also employed to the docked ligand-target complex to explore the stability of ligand-target complex, improve docking results, and analyze the molecular mechanisms of protein-target interactions.
Design, synthesis, anti-acetylcholinesterase evaluation and molecular modelling studies of novel coumarin-chalcone hybrids

Hasan AH, Shakya S, Hussain FHS, Murugesan S, Chander S, Pratama MRF, et al.

J Biomol Struct Dyn, 2023;41(21):11450-11462.
PMID: 36591704 DOI: 10.1080/07391102.2022.2162583

The major enzyme responsible for the hydrolytic breakdown of the neurotransmitter acetylcholine (ACh) is acetylcholinesterase (AChE). Acetylcholinesterase inhibitors (AChEIs) are the most prescribed class of medications for the treatment of Alzheimer's disease (AD) and dementia. The limitations of available therapy, like side effects, drug tolerance, and inefficacy in halting disease progression, drive the need for better, more efficacious, and safer drugs. In this study, a series of fourteen novel chalcone-coumarin derivatives (8a-n) were designed, synthesized and characterized by spectral techniques like FT-IR, NMR, and HR-MS. Subsequently, the synthesized compounds were tested for their ability to inhibit acetylcholinesterase (AChE) activity by Ellman's method. All tested compounds showed AChE inhibition with IC50 value ranging from 0.201 ± 0.008 to 1.047 ± 0.043 μM. Hybrid 8d having chloro substitution on ring-B of the chalcone scaffold showed relatively better potency, with IC50 value of 0.201 ± 0.008 μM compared to other members of the series. The reference drug, galantamine, exhibited an IC50 at 1.142 ± 0.027 μM. Computational studies revealed that designed compounds bind to the peripheral anionic site (PAS), the catalytic active site (CAS), and the mid-gorge site of AChE. Putative binding modes, ligand-enzyme interactions, and stability of the best active compound are studied using molecular docking, followed by molecular dynamics (MD) simulations. The cytotoxicity of the synthesised derivatives was determined using the MTT test at three concentrations (100 g/mL, 500 g/mL, and 1 mg/mL). None of the chemicals had a significant effect on the body at the highest dose of 1 mg/mL.Communicated by Ramaswamy H. Sarma.
Fulltext Adverse events related to COVID-19 vaccines: the need to strengthen pharmacovigilance monitoring systems

Shrestha S, Khatri J, Shakya S, Danekhu K, Khatiwada AP, Sah R, et al.

Drugs Ther Perspect, 2021;37(8):376-382.
PMID: 34366660 DOI: 10.1007/s40267-021-00852-z

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new species of β-coronavirus genus named severe acute respiratory syndrome coronavirus 2. The COVID-19 pandemic, which started in late 2019 and continues as at mid-2021, has caused enormous damage to health and lives globally. The urgent public health need has led to the development of vaccines against COVID-19 in record-breaking time. The COVID-19 vaccines have been widely rolled out for the masses by many countries following approval for emergency use by the World Health Organization and regulatory agencies in many countries. In addition, several COVID-19 vaccine candidates are undergoing clinical trials. However, myths, fears, rumors, and misconceptions persist, particularly in regard to adverse events. In this commentary, we describe the adverse events associated with COVID-19 vaccines and discuss why it is essential to have a functional adverse event monitoring system in this context.
Novel thiophene Chalcones-Coumarin as acetylcholinesterase inhibitors: Design, synthesis, biological evaluation, molecular docking, ADMET prediction and molecular dynamics simulation

Hasan AH, Murugesan S, Amran SI, Chander S, Alanazi MM, Hadda TB, et al.

Bioorg Chem, 2022 02;119:105572.
PMID: 34971946 DOI: 10.1016/j.bioorg.2021.105572

A series of around eight novel chalcone based coumarin derivatives (23a-h) was designed, subjected to in-silico ADMET prediction, synthesized, characterized by IR, NMR, Mass analytical techniques and evaluated as acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer's disease (AD). The results of predicted ADMET study demonstrated the drug-likeness properties of the titled compounds with developmental challenges in lipophilicity and solubility parameters. The in vitro assessment of the synthesized compounds revealed that all of them showed significant activity (IC50 ranging from 0.42 to 1.296 µM) towards AChE compared to the standard drug, galantamine (IC50 = 1.142 ± 0.027 µM). Among these, compound 23e displayed the most potent inhibitory activity with IC50 value of 0.42 ± 0.019 µM. Cytotoxicity of all compounds was tested on normal human hepatic (THLE-2) cell lines at three different concentrations using the MTT assay, in which none of the compound showed significant toxicity at the highest concentration of 1000 µg/ml compared to the control group. Based on the docking study against AChE, the most active derivative 23e was orientated towards the active site and occupied both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the target enzyme. In-silico studies revealed tested showed better inhibition activity of AChE compared to Butyrylcholinesterase (BuChE). Molecular dynamics simulation explored the stability and dynamic behavior of 23e- AChE complex.