Aparoop Das

Synthesis and Antibacterial Assessment of N-[4-(4-substituted phenyl)-1,3-thiazol-2-yl]-1,3,5-triazin-2-amine.

In a wide search program towards new and efficient antibacterial agents, we assessed the extent to which physicochemical properties can be exploited to promote antibacterial activity associated with a series of substituted s-triazine. The synthesized compounds (1a-12b) were subsequently screened for their in vitro antibacterial activity against three gram positive (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus) and three Gram-negative microorganism (Salmonella typhi, Escherichia coli, Klebsiella aerogenes) by the broth dilution technique, recommended by European Committee for antimicrobial susceptibility testing with reference to streptomycin.

Design, synthesis, and in vitro antibacterial screening of some novel 3-pentyloxy-1-hydroxyxanthone derivatives

A series of 3-pentyloxy-1-hydroxyxanthone derivatives were synthesized by four-step reactions: first cyclocondensation between salicylic acid and phloroglucinol in the presence of Eaton’s reagents, then alkylation with 1,5-dibromopentane, followed by nucleophilic substitution by different nucleophiles to obtain final compounds. Molecular structures of the synthesized compounds were elucidated by FT-IR, 1H NMR, 13C NMR, mass spectral data, and elemental analysis. The in vitro antibacterial activity was evaluated by MIC determination using broth dilution method against representative three Gram-positive and three Gram-negative bacterial strains with reference to ofloxacin. All the synthesized compounds showed antibacterial activity; besides the compounds 7f and 7g showed better Gram-positive and Gram-negative antibacterial activities.

Safety evaluation of an oat grain alkaloid gramine by genotoxicity assays

Abstract Gramine is a natural indole alkaloid that has been isolated from different raw plants occurring mainly in Avena sativa, etc. The study was aimed to investigate the possible in vitro antioxidant, in vitro mutagenic, in vitro antimutagenic, and in vivo genotoxic activity of gramine using ferric reducing ability of plasma (FRAP) assay, Metal chelating, Ames bacterial reverse mutation test, and the mouse bone marrow micronucleus assay as well as chromosomal aberration. Four concentrations of gramine viz. 250, 500, 1000, and 2000 μg/mL were evaluated for its antioxidant activity in FRAP Assay and Metal Chelating Test. Four concentrations of gramine (1250 μg/plate, 2500 μg/plate, 5000 μg/plate, and 10 000 μg/plate) were employed in Salmonella typhimurium strains to study the mutagenicity in the presence and absence of standard mutagens, 2-aminofluorene (2-AF), sodium azide (SA), and 2-nitrofluorene (2-NF). Three doses, i.e. 0.1, 0.2, and 0.3 × the LD50 of gramine (i.e. 50 mg/kg, 100 mg/kg, and 150 mg/kg) were administered orally to either sex of Swiss albino mice for 48 h to study the genotoxic activity in micronucleus assay as well as chromosomal aberration. Gramine showed potent antioxidant activity in both the assay. Gramine at the given dose lacks mutagenicity as well as found to possess antimutagenic efficacy. Interestingly, S9 enzymes increase the antimutagenic activity in a dose-dependent manner. There was no significant increase in the frequency of micronucleated polychromatic erythrocytes (MNPCEs), as well as no significant difference in the percentage of chromosomal aberrations was observed between the gramine groups and the negative groups but percentage of polychromatic erythrocytes (PCEs) is found to be higher in all the gramine groups. These results indicate significant antioxidant, non-mutagenic as well as non-genotoxic activity of gramine in vitro and in vivo in the given doses.

Corticosteroids and aldose reductase inhibitor Epalrestat modulates cardiac action potential via Kvβ1.1 (AKR6A8) subunit of voltage-gated potassium channel

We previously demonstrated the role of Kvβ1.1 subunit of voltage-activated potassium channel in heart for its sensory roles in detecting changes in NADH/NAD and modulation of ion channel. However, the pharmacological role for the association of Kvβ1 via its binding to ligands such as cortisone and its analogs remains unknown. Therefore, we investigated the significance of Kvβ1.1 binding to cortisone analogs and AR inhibitor epalrestat. In addition, the aldose reductase (AR) inhibitor epalrestat was identified as a pharmacological target and modulator of cardiac activity via binding to the Kvβ1 subunit. Using a combination of ex vivo cardiac electrophysiology and in silico binding, we identified that Kvβ1 subunit binds and interacts with epalrestat. To identify the specificity of the action potential changes, we studied the sensitivity of the action potential prolongation by probing the electrical changes in the presence of 4-aminopyridine and evaluated the specificity of pharmacological effects in the hearts from Kvβ1.1 knock out mouse. Our results show that pharmacological modulation of cardiac electrical activity by cortisone analogs and epalrestat is mediated by Kvβ1.1.

Preliminary phytochemical screening, in-vitro antioxidant activity, total polyphenolic and flavonoid content of Garcinia lanceifolia Roxb. and Citrus maxima (Burm.) Merr. -

Garcinia lanceifolia and Citrus maxima are two indigenous fruits of East India, particularly Assam; which has been used in various folkloric medicines to treat disorders ranging from diarrhoea and jaundice to stomach and heart problems. The main aim of this study was to establish and compare the antioxidant potential of these two plants. The methanolic extracts of the bark of G. lanceifolia and C. maxima were tested for their antioxidant potential using various established in-vitro assay procedures. The estimation of the total phenolic and total flavonoid content were also carried out. The phytochemical screening was also done prior to these assays, and it revealed that both the extracts were found to contain tannins and phenolic compounds and flavonoids along with other phytoconstituents. The results reveal that both these plants have a considerable amount of antioxidant activity which can be compared with each other and also the standards.

Toward resistance‐compromised DHFR inhibitors part 1: Combined structure/ligand‐based virtual screenings and ADME‐Tox profiling

The front‐line antimalarial drugs, for example, chloroquine, mefloquine, sulfadoxine, pyrimethamine, atovaquone, and artemether, are often failing because of the worldwide spread of drug‐resistant parasites. There has been significant recent interest in virtual screening to drive innovative drug discovery and to combat resistance efforts for a wide range of diseases. In fact, virtual screening has become the “gold standard” for major pharmaceutical industries and some university groups. Therefore, we present herein a structure‐based LibDock/CHARMM modeling and a set of appropriate scoring function evaluation criteria: correlation, consensus score, correlation‐based score, generally applicable replacement for root‐mean‐square deviation using a training set of 38 phenylthiazolyl‐1,3,5‐triazines from our previous reports and followed by a ligand‐based model to identify molecular features like hydrogen‐bond acceptor, hydrogen‐bond donor, hydrophobicity, and ring aromatic (RA) using Catalyst HipHop/HypoGen module. Next, TOPKAT module was applied to predict ADME‐Tox properties. The combined structure/ligand‐based approaches inadvertently arrived at a conserved Arg122 binding site from reliable LigScore1_dreiding top scoring function and are subsequently attributed to reserve important interactions and combat mutational drug resistance. The best pharmacophore model suggested that 1 hydrogen‐bond acceptor, 2 hydrophobicities, and 1 ring aromatic feature with good sensitivity at 0.50, specificity at 0.66, enrichment at 1.60, and accuracy at 0.50. Finally, good pharmacokinetics, metabolic stability, and toxicity endpoints were predicted in the comparison of proguanil and cycloguanil. These druggability insights are useful for researchers to deliver more effective, safer, both wild‐type and resistance‐compromised, and more economical dihydrofolate reductase inhibitors in the near future.

Design, synthesis and antibacterial activity of substituted phenylthiazolyl s-triazines

Substituted s-triazine derivatives are believed to exert their antibacterial effects by nonspecific mechanisms. We have assessed the extent to which physicochemical properties can be used to promote discriminative activity of these compounds. In the search for new and efficient antibacterial agents, a series of substituted phenylthiazolyl s-triazines were synthesized and screened for their in vitro antibacterial activity against three Gram positive (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus) and three Gram-negative (Salmonella typhi, Escherichia coli, Klebsiella aerogenes) bacterial species by the broth dilution technique as recommended by European Committee for antimicrobial susceptibility testing (EUCAST) with reference to streptomycin.