Anand K. Halve

Synthesis and in vitro antimicrobial studies of some new 3-[phenyldiazenyl] benzaldehyde N-phenyl thiosemicarbazones

The increasing clinical importance of drug resistant microbial pathogens has lent additional urgency to microbiological research and new antimicrobial compound development. For this purpose, a new series of 3-[phenyldiazenyl] benzaldehyde N-phenylthiosemicarbazones were synthesized and evaluated for antifungal and antibacterial activity. The reaction of 2-hydroxy-5-[phenyldiazenyl] benzaldehyde (I) with N-phenylhydrazinecarbothioamide (II) were carried out in DMF. The antimicrobial activity of the synthesized target compounds (III) were evaluated by screening on different human pathogens using the disc diffusion assay. All the compounds exhibited considerable inhibition against the bacteria and fungi tested.

Controlled drug delivery of antileishmanial chalcones from Layer-by-Layer (LbL) self assembled PSS/PDADMAC thin films

Layer-by-Layer (LbL) approach was applied for the encapsulation of antileishmanial drugs viz. chalcones (3-mB-4′-HC and 3-DC-4′-HC) to study their release properties at pH 7.4 from a polyelectrolyte self assembled multilayer thin film. The LbL self assembly was achieved by alternate adsorption of oppositely charged polyelectrolytes, poly(styrene-4-sulfonic acid) sodium salt (PSS) and poly(diallyldimethylammonium) chloride (PDADMAC) on planar quartz substrate. The growth of the multilayer self assembly as well as loading and release of the drugs were studied by UV-Visible spectroscopy. Both the chalcones, 3-mB-4′-HC and 3-DC-4′-HC have shown controlled and sustained release up to 224 and 824 minutes respectively. Kinetic fitting of the data confirmed that the process of drug release from the self assembly followed pseudo second order kinetics (R2 ≥ 0.99).

Synthesis and in vitro kinetic study of novel mono-pyridinium oximes as reactivators of organophosphorus (OP) inhibited human acetylcholinesterase (hAChE)

A series of mono pyridinium oximes linked with arenylacetamides as side chains were synthesized and their in vitro reactivation potential was evaluated against human acetylcholinesterase (hAChE) inhibited by organophosphorus inhibitors (OP) such as sarin, VX and tabun. The reactivation data of the synthesized compounds were compared with those obtained with standard reactivators such as 2-PAM and obidoxime. The dissociation constant (KD) and specific reactivity (kr) of the oximes were also determined by performing reactivation kinetics against OP inhibited hAChE. Among the synthesized compounds, oximes 1-(2-(4-cyanophenylamino)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium chloride (12a) and 4-((hydroxyimino)methyl)-1-(2-(4-methoxyphenylamino)-2-oxoethyl)pyridinium chloride (2a) were found most potent reactivators for hAChE inhibited by sarin. In case of VX inhibited hAChE majority of the oximes have shown good reactivation efficacies. Among these oximes 1-(2-(benzylamino)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium chloride (18a), 4-((hydroxyimino)methyl)-1-(2-(4-(methoxycarbonyl)phenylamino)-2-oxoethyl)pyridinium-chloride (14a) and 12a were found to surpass the reactivation potential of 2-PAM and obidoxime. However, the synthesized oximes showed marginal reactivation efficacies in case of tabun inhibited hAChE. The pKa value of the oximes were determined and correlated with their observed reactivation potential.

Controlled release studies of antimalarial 1, 3, 5-trisubstituted-2-pyrazolines from biocompatible chitosan-heparin Layer-by-Layer (LbL) self assembled thin films.

Herein we report the in-vitro controlled release properties of 1, 3, 5-trisubstituted-2-pyrazolines through Layer-by-Layer (LbL) self assembled thin films fabricated from chitosan and heparin sodium salt as biocompatible polyelectrolytes. This study was carried out as a preliminary step towards the applicability of LbL technique in prophylactic drug delivery of antimalarial drugs. The growth of LbL self assembly was monitored by UV-Visible spectrophotometry and Quartz Crystal Microbalance (QCM). The loading as well as in-vitro release studies (in phosphate buffer saline at pH 7.4) were carried out using UV-Visible spectroscopy. Three compounds having good antimalarial activity were tested and the release rate was found inversely proportional to the hydrophobicity of the drug. Pzln-4 has shown best release among all the three compounds (up to 780 min) followed by Pzln-5 and Pzln-8. The release trend was that of a fast release up to first 2 h followed by a steady release. Kinetic fitting of the data confirmed the process of drug release followed a pseudo second order kinetics (R(2)≥0.99). A large value of rate constant (k) revealed a faster release. Pzln-4 has shown smallest value of k corresponding to slowest release among all the three compounds.

Synthesis and in vitro kinetic evaluation of N-thiazolylacetamido monoquaternary pyridinium oximes as reactivators of sarin, O-ethylsarin and VX inhibited human acetylcholinesterase (hAChE)

Presently available medications for treatment of organiphosphorus poisoning are not sufficiently effective due to various pharmacological and toxicological reasons. In this regard, herein we report the synthesis of a series of N-thiazolylacetamide monoquaternary pyridinium oximes and its analogs (1a-1b to 6a-6b) with diversely substituted thiazole ring and evaluation of their in vitro reactivation efficacies against nerve agent (sarin, O-ethylsarin and VX) inhibited human erythrocyte acetylcholinesterase (hAChE). Reactivation kinetics was performed to determine dissociation constant (KD), reactivity rate constant (kr) and the second order rate constant (kr2) for all the compounds and compared their efficacies with commercial antidotes viz. 2-PAM and obidoxime. All the newly synthesized oximes were evaluated for their physicochemical parameters (pKa) and correlated with their respective reactivation efficacies to assess the capability of the oxime reactivator. Three of these novel compounds showed promising reactivation efficacies toward OP inhibited hAChE. Molecular docking studies were performed in order to correlate the reactivation efficacies with their interactions in the active site of the AChE.

Synthesis, antimicrobial screening and structure-activity relationship of some novel 2-hydroxy-5-(nitro-substituted phenylazo) benzylidine anilines

The title compounds were synthesized by the condensation of nitro-substituted 2-hydroxy-5- (nitro-substituted phenylazo) benzaldehyde (3) with different aromatic amines in presence of ethanol in good yield. The chemical structures were confirmed by IR, 1H NMR and elemental analysis. All the synthesized compounds (4a-j) have been evaluated for their in vitro antimicrobial activity against S. aureus , P. aeruginosa , E. coli , A. fumigatus , A. niger and C. neoformans .

4-phenyldiazenyl 2-(phenylimino methyl) phenols; synthesis and in-vitro biological evaluation as potential antibacterial agents

A new series of 4-phenyldiazenyl 2-(phenylimino methyl) phenols were synthesized by the condensation of 5-[(2-chloro phenyl) diazenyl] 2-hydroxybenzaldehyde with different substituted aromatic amines and sulphonamides. All the synthesized compounds were screened in-vitro for their antibacterial activity against different human pathogens viz: B. anthracis, E.coli, S. aureus, S. typhimurium, and P. aeruginosa using disk diffusion assay. All the compounds exhibited considerable inhibition against the bacteria tested.

One-pot Multi-component Synthesis of Some Pharmacologically Significant 2,4,5-Tri and 1,2,4,5-Tetrasubstituted Imidazoles: A Review

Heterocyclic compounds are acquiring more importance in recent years because of their pharmacological activities. Compounds containing imidazole moiety have many pharmacological properties and play important role in biochemical processes. Imidazole is a natural compound which exists in many important natural molecules such as the amino acid histidine, vitamin B12, histamine, biotin and purines like adenine and guanine. Imidazole derivatives play significant roles in various pharmacological activities such as anticancer, antibacterial, antifungal, antiviral, anti-HIV and antitubercular. This article aims to review the work in the methods of synthesis using various catalytic system, solvent condition and pharmacological potential of 2,4,5-tri and 1,2,4,5tetrasubstituted imidazoles reported during last 15 years. Review Article Bansal et al.; IRJPAC, 11(4): 1-26, 2016; Article no.IRJPAC.24493 2

Synthesis and in vitro screening of N-phenacylpyridinium oximes as reactivators of organophosphorus (OP)-inhibited electric eel acetylcholinesterase (AChE)

Pyridinium oxime-based drugs are generally used in the treatment of acute organophosphorus (OP) nerve agent poisoning. In this regard, a series of mono-pyridinium oximes bearing substituted phenacyl moieties as side chain were synthesized and screened for their in vitro reactivation efficacies against electric eel acetylcholinesterase (AChE) inhibited by OP inhibitors such as DFP, sarin and VX. The results of the in vitro reactivation data of the synthesized compounds were compared to standard antidotes 2-PAM and obidoxime. Among the synthesized compounds, 1a, 2a, 7a, 8a, 11a, 12a, 13a, 14a and 16a have shown better reactivation efficacy than 2-PAM and obidoxime against VX-inhibited AChE. Oximes 8a, 8b, 11a and 12a were at par with obidoxime in the reactivation of sarin-inhibited AChE. The pKa values for all the oximes were determined and correlated with their observed reactivation potential.

The effect of aryl hydrazono ester containing dipeptides (AHEDs) on mosquito egg-laying behaviour

A series of novel aryl hydrazono ester containing dipeptides (AHEDs) were synthesized by using polystyrene-supported 2-isobutoxy-1-isobutoxycarbonyl-1,2-dihydro-quinoline (PS-IIDQ) to study the oviposition responses in Aedes albopictus mosquitoes at 1 ppm and 10 ppm concentrations. Two different synthetic routes have been optimized successfully for the synthesis of target compounds. The pheromone and semiochemical mediated oviposition activity of mosquitoes is a well-known aspect in mosquito behavioral ecology. Structural elucidation of synthesized AHED was achieved by spectral analysis. In a dual choice experiment, the oviposition responses of gravid A. albopictus were evaluated against AHED-1 to AHED-15 at two different concentrations. Among all the compounds, AHED-6 showed the maximum oviposition attractant activity with an oviposition activity index (OAI) of +0.538 at 10 ppm. In contrast to this, AHED-13 exhibited the highest oviposition deterrent activity with an OAI of −0.774 at 1 ppm.