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QSAR and Pharmacophore Mapping Studies on Benzothiazinimines to Relate their Structural Features with anti-HIV Activity

Geethaavacini G, Poh GP, Yan LY, Deepashini R, Shalini S, Harish R, et al.

Med Chem, 2018;14(7):733-740.
PMID: 29807521 DOI: 10.2174/1573406414666180529091618

BACKGROUND: The development of severe drug resistance caused by the extensive use of anti-HIV agents has resulted in a greatly extensive reduction in these drugs efficacy.
OBJECTIVES: To identify the important pharmacophoric features and correlate 3D chemical structure of benzothiazinimines with their anti-HIV potential using 2D, 3D-QSAR and pharmacophore modeling studies.
METHODS: QSAR and pharmacophore mapping studies have been used to relate structural features. 2D QSAR and 3D QSAR studies were performed using partial least square and k-nearest neighbor methodology, coupled with various feature selection methods, viz. stepwise, genetic algorithm, and simulated annealing, to derive QSAR models which were further validated for statistical significance.
RESULTS: The physicochemical descriptor XAHydrophilicArea and SsOHE-index, and alignmentindependent descriptor T_C_Cl_6 showed significant correlation with the anti-HIV activity of benzothiazinimines in 2D QSAR. 3D QSAR results showed the significant effect of electrostatic and steric field descriptors in the anti-HIV potential of benzothiazinimines. The generated pharmacophore hypothesis demonstrated the importance of aromaticity and hydrogen bond acceptors.
CONCLUSION: The significant models obtained in this study suggested that these techniques could be used as a guidance for designing new benzothiazinimines with enhanced anti-HIV potential.
Mechanistic insights into acyclovir-polyethylene glycol 20000 binary dispersions

Venkateskumar K, Parasuraman S, Gunasunderi R, Sureshkumar K, Nayak MM, Shah SA, et al.

Int J Pharm Investig, 2016 Oct-Dec;6(4):194-200.
PMID: 28123988 DOI: 10.4103/2230-973X.195925

The objective of this study is to provide a mechanistic insight into solubility enhancement and dissolution of acyclovir (ACY) by polyethylene glycol20000 (PEG20000).
Acyclovir-Polyethylene Glycol 6000 Binary Dispersions: Mechanistic Insights

Venkateskumar K, Parasuraman S, Gunasunderi R, Sureshkumar K, Nayak MM, Shah SAA, et al.

AAPS PharmSciTech, 2017 Aug;18(6):2085-2094.
PMID: 28004342 DOI: 10.1208/s12249-016-0686-9

The dissolution and subsequent oral bioavailability of acyclovir (ACY) is limited by its poor aqueous solubility. An attempt has been made in this work to provide mechanistic insights into the solubility enhancement and dissolution of ACY by using the water-soluble carrier polyethylene glycol 6000 (PEG6000). Solid dispersions with varying ratios of the drug (ACY) and carrier (PEG6000) were prepared and evaluated by phase solubility, in vitro release studies, kinetic analysis, in situ perfusion, and in vitro permeation studies. Solid state characterization was done by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analysis, and surface morphology was assessed by polarizing microscopic image analysis, scanning electron microscopy, atomic force microscopy, and nuclear magnetic resonance analysis. Thermodynamic parameters indicated the solubilization effect of the carrier. The aqueous solubility and dissolution of ACY was found to be higher in all samples. The findings of XRD, DSC, FTIR and NMR analysis confirmed the formation of solid solution, crystallinity reduction, and the absence of interaction between the drug and carrier. SEM and AFM analysis reports ratified the particle size reduction and change in the surface morphology in samples. The permeation coefficient and amount of ACY diffused were higher in samples in comparison to pure ACY. Stability was found to be higher in dispersions. The results suggest that the study findings provided clear mechanical insights into the solubility and dissolution enhancement of ACY in PEG6000, and such findings could lay the platform for resolving the poor aqueous solubility issues in formulation development.
Fulltext Effect of L-Carnosine in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis

Sureshkumar K, Durairaj M, Srinivasan K, Goh KW, Undela K, Mahalingam VT, et al.

Front Biosci (Landmark Ed), 2023 Jan 18;28(1):18.
PMID: 36722274 DOI: 10.31083/j.fbl2801018

INTRODUCTION: L-carnosine has been found to have multimodal activity.
AIM: The aim of this review was to find out the efficacy of L-carnosine in patients with age-related diseases.
METHODS: Clinical studies evaluated the effect of L-carnosine on cancer, cardiovascular disease, diabetes, and neurodegenerative disorders were searched in electronic bibliographic databases. The protocol has been registered with PROSPERO (CRD42022314033). The revised Cochrane risk of bias tool for randomized trials was used to assess all of the reports for risk of bias. RevMan 5.4 was used to conduct the meta-analysis.
RESULTS: Following the screening process, 14 papers were selected for systematic review, with 9 of them being qualified for meta-analysis. Many of the included studies showed that L-carnosine has potential therapeutic activity in age related diseases. Results from the meta-analysis showed that in diabetes mellitus, HbA1c [mean difference (MD) 95% CI = -1.25 (-2.49, -0.022); p = 0.05; p = 0.001; I2 = 85%] and fasting blood sugar (FBS) [MD 95% CI = -12.44 (-22.44, -2.44); p = 0.01; p = 0.40; I2 = 0%] and in neurodegenerative disorder, Wechsler Memory Scale Logical Memory 2 (WMS-LM2) [MD 95% CI = 1.34 (0.83, 1.85); p < 0.00001; p = 0.43; I2 = 0%], showed statistically significant difference, favoring the L-carnosine group over the control group. While in neurodegenerative disorder, Alzheimer 's Disease Assessment Scale (ADAS) [MD 95% CI = 0.98 (-1.55, -0.42); p = 0.0007; p = 0.86; I2 = 0%] and Back Depression Inventory (BDI) [MD 95% CI = -1.12 (-1.87, -0.37); p = 0.003; p = 0.73; I2 = 0%] showed statistically significant difference, favoring the control group over L-carnosine group.
CONCLUSIONS: Clinical studies were conducted to manage chemotherapy induced toxicities and there are no clinical studies available for its anti-cancer use, and the current evidence does not support its use in the treatment of cardiovascular disease.