Anurag Khatkar

Design, synthesis, antimicrobial, anticancer evaluation, and QSAR studies of 4-(substituted benzylidene-amino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-ones

A series of 4-(substituted benzylidene-amino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-ones (1–17) was synthesized and tested in vitro for its antimicrobial and anticancer potentials. The biological screening results indicated that compounds having m-chloro substituent on benzaldehyde portion showed antimicrobial potential, whereas compounds having chloro, methoxy, and hydroxyl groups showed anticancer potential. The quantitative structure activity relationship (QSAR) studies indicated the importance of topological parameter, valence first order molecular connectivity index in describing antifungal activity. The developed QSAR models, however, were statistically insignificant with reference to anticancer activity of the synthesized compounds.

Self Emulsifying Drug Delivery System (SEDDS) for Phytoconstituents: A Review

The self emulsifying drug delivery system (SEDDS) is considered to be the novel technique for the delivery of lipophillic plant actives. The self emulsifying (SE) formulation significantly enhance the solubility and bioavailability of poorly aqueous soluble phytoconstituents. The self emulsifying drug delivery system (SEDDS) can be developed for such plant actives to enhance the oral bioavailability using different excipients (lipid, surfactant, co solvent etc.) and their concentration is selected on the basis of pre formulation studies like phase equilibrium studies, solvent capacity of oil for drug and mutual miscibility of excipients. The present review focuses mainly on the development of SEDDS and effect of excipients on oral bioavailability and aqueous solubility of poorly water soluble phytoconstituents/ derived products. A recent list of patents issued for self emulsifying herbal formulation has also been included. The research data for various self emulsifying herbal formulation and patents issued were reviewed using different databases such as PubMed, Google Scholar, Google patents, Scopus and Web of Science. In a nutshell, we can say that SEDDS was established as a novel drug delivery system for herbals and with the advances in this technique, lots of patents on herbal SEDDS can be translated into the commercial products.

Design, synthesis, and biological evaluation of thiourea and guanidine derivatives of pyrimidine-6-carboxylate

Two new series of methyl 7-methyl-5-(substituted-phenyl)-3,5-dihydro-2H—substituted [3,2-α]pyrimidine-6-carboxylate derivatives of thiourea and guanidine were synthesized. These compounds were characterized and evaluated for their antibacterial activity against Staphylococcus aureus, Bacillussubtilis, Escherichiacoli, and antifungal Aspergillus niger and Candida albicans and free radical scavenging activity using DPPH reagent method. Compound 7f was found to be the most active antibacterial and antifungal agent comparable to the standard drugs ciprofloxacin and fluconazole. Further, the compounds 5e, 7g, and 7h were also found to have significant antimicrobial activity. Compound 5a was found to be the most active antioxidant among all the targeted compounds, while compounds 5b, 5g, 7b, and 7f also had significant antioxidant activity compared to standard ascorbic acid.

Synthesis and biological evaluation of thiazolo and imidazo N-(4-nitrophenyl)-7-methyl-5-aryl-pyrimidine-6 carboxamide derivatives

Two new series of thiazolo and imidazo N-(4-nitrophenyl)-7-methyl-5-aryl-pyrimidine-6 carboxamide derivatives were synthesized. All the synthesized compounds were evaluated for their antimicrobial activity against Gram-positive bacteria: Staphylococcusaureus MTCC 3160, Bacillus subtilis MTCC 441, Gram-negative bacterium: Escherichia coli MTCC 443 and antifungal activity against Candida albicans MTCC 227 and Aspergillusniger MTCC 281 and free radical scavenging activity. Compound 7e was found the most active antimicrobial comparable to standards taken. Compounds 7a, 7c, 9a, and 9d also showed significant antibacterial and antifungal activity. Further, compounds 7f, 9d, and 9h showed significant antioxidant activity with IC50 comparable with the standard compound. The synthesized compounds were confirmed for their structure by means of various spectrometric techniques like IR, 1H NMR, mass, and elemental analysis.

Synthesis, photoluminescence and biological properties of terbium(III) complexes with hydroxyketone and nitrogen containing heterocyclic ligands.

The ternary terbium(III) complexes [Tb(HDAP)3⋅biq], [Tb(HDAP)3⋅dmph] and [Tb(HDAP)3⋅bathophen] were prepared by using methoxy substituted hydroxyketone ligand HDAP (2-hydroxy-4,6-dimethoxyacetophenone) and an ancillary ligand 2,2-biquinoline or 5,6-dimethyl-1,10-phenanthroline or bathophenanthroline respectively. The ligand and synthesized complexes were characterised based on elemental analysis, FT-IR and (1)H NMR. Thermal behaviour of the synthesized complexes illustrates the general decomposition patterns of the complexes by thermogravimetric analysis. Photophysical properties such as excitation spectra, emission spectra and luminescence decay curves of the complexes were investigated in detail. The main green emitting peak at 548nm can be attributed to (5)D4→(7)F5 of Tb(3+) ion. Thus, these complexes might be used to make a bright green light-emitting diode for display purpose. In addition the in vitro antibacterial activities of HDAP and its Tb(III) complexes against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and antifungal activities against Candida albicans and Aspergillus niger are reported. The Tb(3+) complexes were found to be more potent antimicrobial agent as compared to the ligand. Among all these complexes, [Tb(HDAP)3⋅bathophen] exhibited excellent antimicrobial activity which proves its potential usefulness as an antimicrobial agent. Furthermore, in vitro antioxidant activity tests were carried out by using DPPH method which indicates that the complexes have considerable antioxidant activity when compared with the standard ascorbic acid.

Regulatory perspectives on medical device approval in global jurisdictions

Today medical device sector is evolving to find the new horizons. Medical device approval is a time-consuming process that requires submission of safety, efficacy and quality documentation to national regulatory bodies in various countries. While there are some similarities among the countries regarding medical device regulations, some differences also exist that significantly affect the regulatory scrutiny. This presents a great problem for manufacturers marketing their products in multiple countries. Competent authorities worldwide have begun to realize the problem and collaborate to harmonize the regulations. In the present article regulatory approval procedure is discussed in different jurisdictions such as United States, European Union, Japan, China and India along with comparisons in terms of classification of devices, competent authorities, rules and regulations and quality management systems involved in these countries.

Evaluation of preservative effectiveness of p-coumaric acid derivatives in aluminium hydroxide gel-USP

Background: Deterioration of pharmaceutical preparations due to growth of microorganisms is a great challenge and need of preservation becomes very important. Literature reports about various problems associated with the existing synthetic preservatives such as development of microbial resistance (in due course of time) and several serious side effects. Aim: The aim of the present study is to find out new preservatives synthesized from natural sources, which may have better efficiency than the existing synthetic preservatives. The derivatives of naturally occurring p-coumaric acid were subjected for their preservative efficacy study. Their preservative efficiency was evaluated and compared with the standard parabens. Materials and Methods: The selected amide, anilide and ester derivatives of p-coumaric acid were subjected to preservative efficacy testing in an official antacid preparation, (aluminium hydroxide gel-USP) against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans and Aspergillus niger as representative challenging microorganisms as per USP 2004 guidelines. Results: The selected derivatives were found to be effective against all selected strains and showed preservative efficacy comparable to that of standard and even better in case E. coli, C. albicans and A. niger. The 8-hydroxy quinoline ester derivative showed better preservative efficacy than standard as well as other derivatives. Conclusion: The newly synthesized p- coumaric acid preservatives were found to be effective in the proposed pharmaceutical preparation (Aluminium Hydroxide Gel - USP). Also, the synthesized preservatives have shown comparative and even better efficacy than the existing parabens and hence they have potential for use in pharmaceutical preparations.

Virtual Screening of Novel Glucosamine-6-Phosphate Synthase Inhibitors

BACKGROUND Infections caused by microorganisms are the major cause of death today. The tremendous and improper use of antimicrobial agents leads to antimicrobial resistance. AIM AND OBJECTIVE Various currently available antimicrobial drugs are inadequate to control the infections and lead to various adverse drug reactions. Efforts based on computer-aided drug design (CADD) can excavate a large number of databases to generate new, potent hits and minimize the requirement of time as well as money for the discovery of newer antimicrobials. Pharmaceutical sciences also have made development with advances in drug designing concepts. The current research article focuses on the study of various G-6-P synthase inhibitors from literature cited molecular database. Docking analysis was conducted and ADMET data of various molecules was evaluated by Schrodinger Glide and PreADMET software, respectively. Here, the results presented efficacy of various inhibitors towards enzyme G-6-P synthase. Docking scores, binding energy and ADMET data of various molecules showed good inhibitory potential toward G-6-P synthase as compared to standard antibiotics. This novel antimicrobial drug target G-6-P synthase has not so extensively been explored for its application in antimicrobial therapy, so the work done so far proved highly essential. This article has helped the drug researchers and scientists to intensively explore about this wonderful antimicrobial drug target. MATERIALS AND METHODS The Schrodinger, Inc. (New York, USA) software was utilized to carry out the computational calculations and docking studies. The hardware configuration was Intel® core (TM) i5-4210U CPU @ 2.40GHz, RAM memory 4.0 GB under 64-bit window operating system. The ADMET data was calculated by using the PreADMET tool (PreADMET ver. 2.0). All the computational work was completed in the Laboratory for Enzyme Inhibition Studies, Department of Pharmaceutical Sciences, M.D. University, Rohtak, INDIA. RESULTS Molecular docking studies were carried out to identify the binding affinities and interaction between the inhibitors and the target proteins (G-6-P synthase) by using Glide software (Schrodinger Inc. U.S.A.-Maestro version 10.2). Grid-based Ligand Docking with Energetic (Glide) is one of the most accurate docking softwares available for ligand-protein, protein-protein binding studies. A library of hundreds of available ligands was docked against targeted proteins G-6-P synthase having PDB ID 1moq. Results of docking are shown in Table 1 and Table 2. Results of G-6-P synthase docking showed that some compounds were found to have comparable docking score and binding energy (kj/mol) as compared to standard antibiotics. Many of the ligands showed hydrogen bond interaction, hydrophobic interactions, electrostatic interactions, ionic interactions and π- π stacking with the various amino acid residues in the binding pockets of G-6-P synthase. CONCLUSION The docking study estimated free energy of binding, binding pose andglide score and all these parameters provide a promising tool for the discovery of new potent natural inhibitors of G-6-P synthase. These G-6-P synthase inhibitors could further be used as antimicrobials. Here, a detailed binding analysis and new insights of inhibitors from various classes of molecules were docked in binding cavity of G-6-P synthase. ADME and toxicity prediction of these compounds will further accentuate us to study these compounds in vivo. This information will possibly present further expansion of effective antimicrobials against several microbial infections.

In-silico Design and ADMET Studies of Natural Compounds as Inhibitors of Xanthine Oxidase (XO) Enzyme

BACKGROUND Xanthine oxidase a ubiquitous enzyme has been found to be involved in various pathological disorders including gout, hyperuricemia, inflammation, oxidative stress and cardiovascular diseases. Inhibitors of xanthine oxidase thus find a crucial role in the therapeutic treatment of these deadly diseases. OBJECTIVE Considering the side effects of todays treatment regimen here we choose nature based compounds to act as xanthine oxidase inhibitors. In the present work, we performed in-silico docking of natural compounds to reveal the underlying mechanism of inhibition of xanthine oxidase. Further filtration of screened compounds with ADMET studies has been performed. METHOD An in-house library of natural compounds screened through ADMET profile for the drug likeliness property was approached for docking studies using Schrödinger suite. Calculation of docking score was done by glide module and free binding energy calculations were performed through MM/GBSA software. RESULTS Natural leads having better pharmacokinetic profile and mechanism of inhibition were obtained. Docking score, binding energy and different forces involved in interaction were calculated for the top-ranked molecules and good comparison with the standard drugs was achieved Conclusion: Compounds having potential therapeutic activity with low systematic toxicity has been identified against xanthine oxidase which could serve as pharmacophore for the design and synthesis of new drug-like molecules.

Docking-Related Survey on Natural-Product-Based New Monoamine Oxidase Inhibitors and Their Therapeutic Potential

BACKGROUND This is an exciting period for research on monoamine oxidase and its effects on central nervous system. As the current hitting-one-target, therapeutic strategy has become quite inefficient for the treatment of various neurological disorders Objective: The objective of this review is to identify and critically discuss the computational development of multi-target natural and related ligand-MAO protein docking approaches in the study of monoamine oxidase (MAO) enzymes. DISCUSSION Computational development of the new compounds from natural and related synthetic origin, active as MAO inhibitors (MAOIs) was discussed in some detail. The docking studies related to the alkaloids and their various categories secondary metabolites from plants like alkaloids, flavonoids and xanthones class of compounds specially caffeine, β-carboline, naphthoquinone, morpholine, piperine, amphetamine and furthermore curcumin, eugenol, trans-Farnesol and many other extracted plant constituents with their docking studies were discussed in detail. CONCLUSION It is apparent that, by this computational docking approach, more selective, reversible and potent molecules could be proposed as MAO inhibitors by precise modifications on the basic scaffold.