EVALUATION OF ANTISTRESS ACTIVITY OF EXTRACT OF TINOSPORA CORDIFOLIA & ASPARAGUS RACEMOSUS IN RATS

Objectives: Present study was undertaken to evaluate the adaptogenic and antistress activity of T. cordifolia & A.racemosus we investigated the antistress activity of T. cordifolia and A. racemosus by Cold Water Swim Stress Model in rats. Materials and Methods: The anti-stress activity was evaluated on Cold Water Swim Stress induced biochemical changes. Extract of T.cordifolia and A.racemosus was administered orally 400 mg /kg.b.wt. Diazepam (5 mg/ kg.b.wt was used as a gold standard. Serum lipid, serum glucose, plasma cortisol, plasma glutathione total plasma NO and lipid peroxidation in terms of MDA were used as the stress indices. Results: The level of total plasma nitric oxide, (NO), MDA, a lipid peroxidation marker and cortisol were significantly higher in rats with chronic stress compared with healthy control group (p<0.005). Both extract of T.cordifolia and A.racemosus reduced Stress induced lipid peroxide, serum glucose, and serum triglyceride and significantly enhance the plasma glutathione level compared with stress control group (p <0.005). Conclusion: The present findings strongly suggested that oxidative stress plays a significant role in the pathophysiology of chronic stress. The findings of the present study indicate that the herbal agents T.cordifolia and A.racemosus has significant antistress and adaptogenic activity as shown by its mitigating effects on several chronic stress induced biochemical perturbations, comparable to that induced by the well known antistress agent Diazepam

Chemometric QSAR Modeling and In Silico Design of Antioxidant NO Donor Phenols

An acceleration of free radical formation within human system exacerbates the incidence of several life-threatening diseases. The systemic antioxidants often fall short for neutralizing the free radicals thereby demanding external antioxidant supplementation. Therein arises the need for development of new antioxidants with improved potency. In order to search for efficient antioxidant molecules, the present work deals with quantitative structure-activity relationship (QSAR) studies of a series of antioxidants belonging to the class of phenolic derivatives bearing NO donor groups. In this study, several QSAR models with appreciable statistical significance have been reported. Models were built using various chemometric tools and validated both internally and externally. These models chiefly infer that presence of substituted aromatic carbons, long chain branched substituents, an oxadiazole-N-oxide ring with an electronegative atom containing group substituted at the 5 position and high degree of methyl substitutions of the parent moiety are conducive to the antioxidant activity profile of these molecules. The novelty of this work is not only that the structural attributes of NO donor phenolic compounds required for potent antioxidant activity have been explored in this study, but new compounds with possible antioxidant activity have also been designed and their antioxidant activity has been predicted in silico

Molecular Modeling on Structure-Function Analysis of Human Progesterone Receptor Modulators

Considering the significance of progesterone receptor (PR) modulators, the present study is explored to envisage the biophoric signals for binding to selective PR subtype-A using ligand-based quantitative structure activity relationship (QSAR) and pharmacophore space modeling studies on nonsteroidal substituted quinoline and cyclocymopol monomethyl ether derivatives. Consensus QSAR models (Training set (Tr): nTr=100, R2pred=0.702; test set (Ts): nTs=30, R2pred=0.705, R2m=0.635; validation set (Vs): nVs=40, R2pred=0.715, R2m=0.680) suggest that molecular topology, atomic polarizability and electronegativity, atomic mass and van der Waals volume of the ligands have influence on the presence of functional atoms (F, Cl, N and O) and consequently contribute significant relations on ligand binding affinity. Receptor independent space modeling study (Tr: nTr=26, Q2=0.927; Ts: nTs=60, R2pred=0.613, R2m=0.545; Vs: nVs=84, R2pred=0.611, R2m=0.507) indicates the importance of aromatic ring, hydrogen bond donor, molecular hydrophobicity and steric influence for receptor binding. The structure-function characterization is adjudged with the receptor-based docking study, explaining the significance of the mapped molecular attributes for ligand-receptor interaction in the catalytic cleft of PR-A

Coupled Phonons, Magnetic Excitations and Ferroelectricity in AlFeO3: Raman and First-principles Studies

We determine the nature of coupled phonons and magnetic excitations in AlFeO3 using inelastic light scattering from 5 K to 315 K covering a spectral range from 100-2200 cm-1 and complementary first-principles density functional theory-based calculations. A strong spin-phonon coupling and magnetic ordering induced phonon renormalization are evident in (a) anomalous temperature dependence of many modes with frequencies below 850 cm-1, particularly near the magnetic transition temperature Tc ~ 250 K, (b) distinct changes in band positions of high frequency Raman bands between 1100-1800 cm-1, in particular a broad mode near 1250 cm-1 appears only below Tc attributed to the two-magnon Raman scattering. We also observe weak anomalies in the mode frequencies at ~ 100 K, due to a magnetically driven ferroelectric phase transition. Understanding of these experimental observations has been possible on the basis of first-principles calculations of phonons spectrum and their coupling with spins

Structure‑based identification of SARS‑CoV‑2 main protease inhibitors from anti‑viral specific chemical libraries : an exhaustive computational screening approach

Worldwide coronavirus disease 2019 (COVID-19) outbreak is still threatening global health since its outbreak first reported in the late 2019. The causative novel virus has been designated as severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2). Although COVID-19 emergent with significant mortality, there is no availability of definite treatment measures. It is now extremely desirable to identify potential chemical entities against SARS-CoV-2 for the treatment of COVID-19. In the present study, a state-of-art virtual screening protocol was implemented on three anti-viral specific chemical libraries against SARS-CoV-2 main protease ( Mpro). Particularly, viewing the large-scale biological role of Mpro in the viral replication process it has been considered as a prospective anti-viral drug target. Herein, on collected 79,892 compounds, hierarchical multistep docking followed by relative binding free energy estimation has been performed. Thereafter, implying a user-defined XP-dock and MM-GBSA cut-off scores as −8.00 and −45.00 kcal/mol, chemical space has been further reduced. Exhaustive molecular binding interactions analyses and various pharmacokinetics profiles assessment suggested four compounds (ChemDiv_D658-0159, ChemDiv_F431-0433, Enamine_Z3019991843 and Asinex_LAS_51389260) as potent inhibitors/modulators of SARS-CoV-2 Mpro. In-depth protein–ligand interactions stability in the dynamic state has been evaluated by 100 ns molecular dynamics (MD) simulation studies along with MM-GBSA-based binding free energy estimations of entire simulation trajectories that have revealed strong binding affinity of all identified compounds towards Mpro. Hence, all four identified compounds might be considered as promising candidates for future drug development specifically targeting the SARS-CoV-2 Mpro; however, they also need experimental assessment for a better understanding of molecular interaction mechanisms.The Deanship of Scientific Research at King Saud University.http://link.springer.com/journal/11030am2022Chemical Patholog

Structure-based identification of galectin-1 selective modulators in dietary food polyphenols : a pharmacoinformatics approach

In this study, a set of dietary polyphenols was comprehensively studied for the selective identification of the potential inhibitors/modulators for galectin-1. Galectin-1 is a potent prognostic indicator of tumor progression and a highly regarded therapeutic target for various pathological conditions. This indicator is composed of a highly conserved carbohydrate recognition domain (CRD) that accounts for the binding affinity of β-galactosides. Although some small molecules have been identified as galectin-1 inhibitors/modulators, there are limited studies on the identification of novel compounds against this attractive therapeutic target. The extensive computational techniques include potential drug binding site recognition on galectin-1, binding affinity predictions of ~ 500 polyphenols, molecular docking, and dynamic simulations of galectin-1 with selective dietary polyphenol modulators, followed by the estimation of binding free energy for the identification of dietary polyphenol-based galectin-1 modulators. Initially, a deep neural network-based algorithm was utilized for the prediction of the druggable binding site and binding affinity. Thereafter, the intermolecular interactions of the polyphenol compounds with galectin-1 were critically explored through the extra-precision docking technique. Further, the stability of the interaction was evaluated through the conventional atomistic 100 ns dynamic simulation study. The docking analyses indicated the high interaction affinity of different amino acids at the CRD region of galectin-1 with the proposed five polyphenols. Strong and consistent interaction stability was suggested from the simulation trajectories of the selected dietary polyphenol under the dynamic conditions. Also, the conserved residue (His44, Asn46, Arg48, Val59, Asn61, Trp68, Glu71, and Arg73) associations suggest high affinity and selectivity of polyphenols toward galectin-1 protein.The Deanship of Scientific Research at Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia, through the Research Groups Program Grant No. (RGP-1440–0021).https://link.springer.com/journal/11030hj2023Chemical Patholog

QSPR with TAU indices: Boiling points of sulfides and thiols

1369-1376The present paper attempts to correlate the boiling points (BP) of 26 thiols and 45 sulfides with different, Topochemically Arrived Unique (TAU) indices (T, TR, F, B, NV, NP, NI NX, NY) in order to explore the utility of the TAU indices in modeling studies. Statistical quality of the relations has been judged by the parameters such as predicted variance (Q2) explained variance (Ra2), correlation coefficient (R), variance ratio (F), etc. The stud y shows that the TAU indices can explain up to 99.7% and predict up  99.6% of the variance of boiling points o f the combined data set. Moreover, the TAU indices can decode specific contributions of molecular bulk (size), functionality, branching and shape parameters to the boiling points of thiols and sulfides. In general, the boiling point increases with increase in bulk and decreases with increase in branching. Further the thiol functionality contributes more to the boiling point than the sulfide functionality

QSPR with TAU indices: Molar refractivity of diverse functional acyclic compounds

1693-1707Molar refractivity of diverse functional acyclic compounds (n = 166) has been correlated with first order TAU indices to unravel the diagnostic feature of the TAU scheme. It has been found that TAU relations could satisfactorily explain the variances of the molar refractivity values of diverse functional compounds (up to 98.6% predicted variance and explained variance for the composite set of 166 compounds), especially when the first order composite topochemical index is partitioned into different components. Moreover, specific contributions of functionality, branching, shape and size terms to the molar refractivity values could be found out from the relations involving TAU parameters. It is observed that molar refractivity increases with the rise in molecular bulk. Further, branching has specific contribution on molar refraction depending on the type of ramification: it has negative contribution to molar refractivity for compounds with same molecular bulk. Negative impact of hydroxy, amino and oxy groups and positive impact of bromo and iodo functionalities on molar refraction are also observed. The predicted MR values based on a selected TAU model are also compared with the calculated MR values according to the Crippen's fragmentation method