Molecular docking and molecular dynamic simulation-based phytoconstituents against SARS-CoV-2 with dual inhibition of the primary protease targets.

A novel coronavirus has caused major health problems and is spreading globally. The main protease enzyme plays a significant role in the number of copies of ss-RNA produced during the proteolytic cleavage of polypeptides. This work aims to find possible dual inhibitors of the 3-Chymotrypsin-like proteases PDB-6W63 and 6LU7 which increase efficiency and faster inhibition activity. By using an in-silico technique, polyphenols are molecularly docked against these targets to inhibit protease enzymes. Some polyphenols, such as pelargonidin and naringin, have significant dual inhibition characteristics with remarkable binding affinities with active scaffolds of both proteins, which have important ADMET parameters. These organic molecules are strongly bonded with amino acids of protein via mostly hydrogen bonding. These polyphenols also have outstanding docking scores and MMGBSA energies. The validity of the docking score was evaluated using a molecular dynamics simulation that assessed the stability of the complex. With the aid of computer-aided drug design, we hypothesise that the dual inhibition of compounds pelargonidin and naringin could effectively and potentially oppose SARS-CoV-2.

Dual targeting in prostate cancer with phytoconstituents as a potent lead: a computational approach for novel drug discovery.

Prostate Cancer (PCa) is an abnormal cell growth within the prostate. This condition is the second most widespread malignancy in elderly males and one of the most frequently diagnosed life-threatening conditions. The Androgen receptor signaling pathway played a crucial role in the initiation and spread to increase the risk of PCa. Hence, targeting the AR receptor signaling pathway is a key strategy for a therapeutic plan for PCa. Our study focuses on recognizing potential inhibitors for dual targeting in PCa by using the in-silico approach. In this study, we target the two enzymes that are CYP17A1 (3RUK) and 5α-reductase (3G1R) responsible for PCa, with the help of phytoconstituents. The natural plant contains various phytochemical types produced from secondary metabolites and used as a medical treatment. The in-silico investigation of phytoconstituents and enzymes was done by approaching molecular docking, ADMET analysis, and high-level molecular dynamic simulation used to assess the stability and binding affinities of the protein-ligand complex. Some phytoconstituents, such as Peonidin, Pelargonidin, Malvidin and Berberine show complex has good molecular interaction with protein. The reliability of the docking scores was examined using a molecular dynamic simulation, which revealed that the complex remained stable throughout the simulation, which ranged from 0 to 200 ns. The selected hits may be effective against CYP17A1 (3RUK) and 5α-reductase (3G1R) (PCa) using a computer-aided drug design (CADD) method, which further enables researchers for upcoming in-vivo and in-vitro research, according to our in-silico approach.Communicated by Ramaswamy H. Sarma.

Imaging & neuropsychological changes in brain with spiritual practice: A pilot study.

BACKGROUND & OBJECTIVES: Some studies have systematically assessed the effects of spiritual practice (SP) on the brain using combined neuropsychological testing and functional imaging. The objective of the present study was to compare imaging and neuropsychological changes in healthy individuals after SP and those with only physical exercise. METHODS: Healthy adult male volunteers, aged 25-45 yr were randomized into two groups. Group 1 (SP group) underwent the SP and group 2 (controls) did brisk walk for 30 min daily. Detailed neuropsychological evaluation, resting-state functional magnetic resonance imaging (fMRI) and brain 99mTc ethyl cysteinate dimer single-photon emission computed tomography (SPECT) were carried out for both groups before and three months after intervention. RESULTS: Post-intervention, resting state fMRI showed increased connections of left precuneus (in the posterior cingulate cortex area of default mode network) in group 1 and increased left frontal connections in group 2. The neuropsychological tests showed significant improvement in 'Speed of Processing' (Digit Symbol Test) in group 1 and in Focused Attention (Trail Making A) in group 2. The SPECT data in group 1 showed significant improvement in perfusion of the frontal areas, with relatively lesser improvement in parietal areas. Group 2 showed significant improvement in perfusion predominantly in parietal areas, as compared to frontal areas. In addition, significantly improved mood was reported by group 1 and not by group 2. INTERPRETATION & CONCLUSIONS: This pilot study shows important functional imaging and neuropsychological changes in the brain with SP.

Design and synthesis of novel diphenyl oxalamide and diphenyl acetamide derivatives as anticonvulsants.

A series of novel N(1) -substituted-N(2) ,N(2) -diphenyl oxalamides 3a-l were synthesized in good yield by stirring diphenylcarbamoyl formyl chloride (2) and various substituted aliphatic, alicyclic, aromatic, heterocyclic amines in DMF and K(2) CO(3) . Also 2-substituted amino-N,N-diphenylacetamides 5a-m were designed by pharmacophore generation and synthesized by stirring 2-chloro-N,N-diphenylacetamide (4) and various substituted amines in acetone using triethyl amine as a catalyst. All the synthesized compounds were screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Neurotoxicity screening and behavioral testing was also carried out. Some of the synthesized test compounds were found to be more potent than the standard drug.

Design and synthesis of 2-(1, 3-dioxoisoindolin-2-yl)-N-(4-oxo-2-substitutedthiazolidin-3-yl) acetamide derivatives as potential anticonvulsant agents.

A series of 2-(1,3-dioxoisoindolin-2-yl)-N-(4-oxo-2-substitutedthiazolidin-3-yl) acetamide derivatives were designed and synthesized using appropriate synthetic route, keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and CNS depressant activities in mice. The synthesized derivatives were examined in the maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (sc-PTZ) induced seizure and neurotoxicity screens and were also evaluated for behavioral activity. All the tested compounds showed protection against MES test indicative of their ability to inhibit the seizure spread.