Surajit Kumar Ghosh

Antimalarial evaluation and docking studies of hybrid phenylthiazolyl-1,3,5-triazine derivatives: A novel and potential antifolate lead for Pf-DHFR-TS inhibition

Present communication deals with the docking study of hybrid phenyl thiazolyl-1,3,5-triazine analogues (1a-36d) on three selected different binding site viz., α, β and γ of wild type Pf-DFHR-TS. In admiration of excellent H-bond scoring, with regard to cycloguanil and to a large extent similar scoring with WR99210, compound 4a, 12b, 21c, 23c, 28d, 29d, 34d, and 35d were selected for in vitro antimalarial activity against 3D7 strain of Plasmodium falciparum. Findings from the study disclose that a significant correlation was exist between in vitro results and in silico prediction (r(2)=0.543). Furthermore, investigation of structure-activity relationships elucidate crucial structural requirement for site specific binding of ligands.

Antimalarial activity and docking studies of novel bi-functional hybrids derived from 4-aminoquinoline and 1,3,5-triazine against wild and mutant malaria parasites as pf-DHFR inhibitor

Bi-functional conjugates comprised of 4-aminoquinoline and 1,3,5-triazine were synthesized through facile synthetic routes. These compounds were rigorously screened for determination of their antimalarial activity against wild and mutant cultured Plasmodium falciparum. The results disclosed that the conjugates have considerable antimalarial activity against both wild and mutant parasites with marked variation on changing the pattern of substitutions. The observed activity profiles were additionally substantiated by docking studies on both wild and quadruple mutant P. falciparum dihydrofolate reductase thymidylate synthase (pf-DHFR-TS).

4-Aminoquinoline-1,3,5-triazine: Design, synthesis, in vitro antimalarial activity and docking studies

A series of hybrid 4-aminoquinoline 1,3,5-triazine derivatives was synthesized and their chemical structure were confirmed by 1H-NMR, 13C-NMR, FT-IR and mass spectrometric analyses. In vitro antimalarial activity of these compounds was evaluated against chloroquine-sensitive (3D-7) and chloroquine resistant (RKL-2) strains of P. falciparum. Results showed that all compounds had considerable antimalarial activity against both the strains and further docking studies were performed on both wild type (1J3I.pdb) and quadruple mutant (N51I, C59R, S108 N, I164L, 3QG2.pdb) pf-DHFR-TS to quantify the structural parameter necessary for the activity.

Synthesis, SAR and antibacterial activity of hybrid chloro, dichloro-phenylthiazolyl-s-triazines

A series of hybrid novel chloro (1a-9a) and dichloro (10b-18b) phenylthiazolyl-s-triazine were synthesized and subsequently subjected to their antibacterial activity against three gram positive viz. Lactobacillus casei (NCIM-2651); Bacillus cereus (NCIM-2458); Staphylococcus aureus (NCIM-2120) and three gram negative viz Salmonella typhimurium (NCIM-2501); Escherichia coli (NCIM-2065); Klebsiella aerogenes (NCIM-2098). The SAR studies around the lead compound revealed that introduction of electron withdrawing groups and amino (-NH-) and mercapto (-S-) linker bridge seemed more promising towards antibacterial activity. Moreover, the virtual Molinspiration screenings are in compliance with Ghoses rule.

In vitro & in vivo Studies on Lornoxicam Loaded Nanoemulsion Gels for Topical Application

The objective of this work was to increase the solubility, in vitro skin permeability of lornoxicam from semisolid topical formulations and also to investigate the in vivo potential of nanoemulsion formulation. Optimized lornoxicam loaded nanoemulsion was prepared successfully by spontaneous self-emulsification method and the size of the stable formulations was found within the range of 102 to 200 nm. The stable nanoemulsion formulations characterized for viscosity, droplet size, transmission electron microscopy (TEM) and refractive index. In vitro permeation rate of nanoemulsion and conventional gel of lornoxicam (LX) were determined. Prmeability parameters like steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio (Er) were significantly increased in nanoemulsion NE8 and the nanogel NG8 as compared to conventional gel (LG). In vivo studies revealed a significant increase in anti-inflammatory effects as compared with conventional gel of LX. The anti-inflammatory effects of formulation NG8 showed a significant increase in percent inhibition value when compared with control, this difference was found to be highly significant (p<0.001). This work shows for the first time that lornoxicam can be formulated into nanoemulsions and may show promise in enhancing solubility and permeation.

In vitro antimalarial activity and molecular docking analysis of 4-aminoquinoline-clubbed 1,3,5-triazine derivatives.

Aims:  Present report describes the in vitro antimalarial activity and docking analysis of seven 4‐aminoquinoline‐clubbed 1,3,5‐triazine derivatives on pf‐DHFR‐TS.

Antidepressants: Current Strategies and Future Opportunities

Recent advances in research on depression have confirmed that it is common, recurrent and disabling mental disorder. Current medication for the treatment of depression have limited efficacy and delayed onset of therapeutic action. In view of the limitation of the current antidepressant pharmaceuticals, tremendous research efforts are ongoing to search for a pharmacological treatment which may improve antidepressive efficacy, onset of action or even both therapeutic parameters. To address these needs, numerous combination therapies that maintain the benefits associated with selective serotonin reuptake inhibitors (SSRIs) but attempts to improve efficacy or reduce side effects by additional mechanism (5-HT₁A, 5-HT₂C) and newer approaches targeting excitatory (glutamate, NMDA, mGluR₂, mGluR₅) or inhibitory aminoacid system (GABA) or peptidergic system(neurokinin1, corticotrophin releasing factor1, melanin concentrating hormone1) have been identified. The goal of this review is to give a brief overview of the major advances in monoamine based treatment strategies and the new emerging approaches in the treatment of depression.

Design, synthesis and SAR exploration of hybrid 4-chlorophenylthiazolyl-s-triazine as potential antimicrobial agents

Two novel series of hybrid class 4-chlorophenylthiazole-s-triazine were synthesized via nucleophilic substitution of 2,4,6-trichloro-1,3,5-triazine with distinguished alkenyl/alkyl/aryl/hetero alkyl–aryl amino and mercapto nucleophiles under nitrogen atmosphere. We identified that the spectrums of antibacterial activity of all tested compounds reveal promising and significant inhibition of gram-positive and gram-negative micro-organisms and the most active compounds, 31d and 32d, were found to be non-toxic in preliminary cytotoxicity assay. We also report that the Molinspiration and Osiris Property Explorer calculations have found a new lead 32d, which binds preferentially to the nuclear receptor to exhibit antibacterial potency.

Development of 4-aminoquinoline-1,3,5-triazine conjugates as potent antibacterial agent through facile synthetic route

A series of novel hybrid 4-aminoquinoline-1,3,5-triazine derivatives were developed and subsequently tested against representative Gram-positive and Gram-negative microorganisms for determination of their antibacterial activity. Screening results indicate that, title molecule exhibit moderate to potent activity in comparison to standard. These hybrid derivatives were synthesized through a facile synthetic routes and structure of reaction intermediates as well as target molecules were recognised with the aid of various spectroscopic techniques viz., FTIR, NMR, mass and elemental analysis.

Solid lipid nanoparticles (SLNs) gels for topical delivery of aceclofenac in vitro and in vivo evaluation.

Solid lipid nanoparticles (SLN) are very potential formulations for topical delivery of anti-inflammatory and anti-arthritic drugs. The solid state of the lipid particles enable efficient drug encapsulation and controlled drug release. In the present study, the evaluation of different formulation parameters based on variation of concentration of lipid and cosurfactant was studied. The SLN gel formulations of the dispersions were compared to the SLN dispersions and with the marketed gel of aceclofenac. The SLNs were prepared by high speed homogenization and ultra-sonication method with fixed amount of aceclofenac (10%) and pluronic F68 (1.5%). The particle size, zeta potential and span of developed formulations was found to be within the range of 123 nm to 323 nm, -12.4 to -18.5 and 0.42 to 0.86 respectively as the lipid concentration was increased from 7.5% to 40%. The highest entrapment efficiency was found to be 75% with the formulation having lipid concentration of 30% and 0.85% of phospholipon 90G. Permeation rate and controlled release property of xanthan gum loaded SLN gel formulations and SLN dispersion was studied through excised pig skin for 24hr. The drug release of SLN gel formulations was better controlled as compare to SLN dispersions. In vivo anti-inflammatory study showed that action of aceclofenac was enhanced for SLN dispersion and gel formulations. The results indicated the superiority of SLN based formulations for topical delivery of aceclofenac.