Mahabir P. Kaushik

Synthesis and Antimalarial Evaluation of Cyclic β-Amino Acid-Containing Dipeptides

This paper describes an efficient synthesis and the antiparasitic evaluation of cyclic β-amino acid-containing dipeptides 3.1-3.6 and 4.1-4.5. The antimalarial properties of all these dipeptides have been evaluated in vitro against Plasmodium falciparum and in vivo against Plasmodium berghai. Compounds 4.4 and 4.5 have been found to be very effective in this respect, with IC50 values of 3.87 and 3.64 μg/mL in the in vitro test, while 4.5 has also been found to be active in the in vivo evaluation.

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 CHARACTERIZATION OF OXIMINO PYRIDOYL PHOSPHONATES

Abstract Oximino pyridoyl phosphonates were synthesised as well as the methiodide of oximino-2-pyridoyl phosphonate. All these compounds along with their intermediates have been characterized by spectro-scopic methods and by elemental analysis.

Unusual reaction of triethylphosphite with pyridoyl chlorides

Abstract Reaction of 2-pyridoyl chloride with triethylphosphite provided a bis-phosphorus compound 2 arising out of Perkow reaction of the initially formed pyridoylphosphonate. However, 3-and 4-pyridoylchlorides with triethylphosphite gave rise to 4 and 6 probably due to ingress of moisture in the reaction medium.

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.

Novel and Efficient Synthesis of N,N-Dialkylaminoand O-alkylphenyl-2-(1-alkyl/phenyl-2-oxopropylidene) Phosphonohydrazido Oximes - Potential Marine Fish Toxin Analogues. Part 2

A novel and efficient method for the synthesis of N,N-dialkylamino/O-alkyl phenyl-2-(1-alkyl/phenyl-2-oxopropylidene) phosphonohydrazido oximes 4 using activated silica has been developed. The reaction involves the condensation of substituted alpha-ketooxime and N,N-dialkylaminophenylphosphonohydrazides or O-alkylphenylphosphonohydrazides and gave the corresponding phosphonohydrazido oximes in excellent yields under mild conditions.

A Novel and Efficient Synthesis of N,N-Dialkylaminoisopropyl- and O-alkylisopropyl-2-(1-alkyl-2-oxopropylidene)phosphonohydrazido Oximes - Potential Marine Fish Toxin Analogues. Part 1

A novel and efficient method for the synthesis of N,N-dialkylaminoisopropyl- and O-alkylisopropyl-2-(1-alkyl-2-oxopropylidene)phosphonohydrazido oximes (4) using activated silica as dehydrating agent has been developed. The reaction involves the condensation of substituted diacetyl monoxime and N,N-dialkylaminoisopropyl-phosphono hydrazide or O-alkylisopropylphosphono hydrazides and gave the corresponding analogues of a naturally occurring fish toxin in excellent yields under mild conditions.

Trichlorocyanuric acid : an efficient reagent for one-pot synthesis of Ptychodiscus brevis (PB-1) toxin and its derivatives

Trichlorocyanuric acid is an efficient regent for simple and one-pot synthesis of dialkyl, N-cycloctylphosphoraamidates (PB-1) and its various derivatives in excellent yields. The procedure is operationally simple and involves the reaction of various dialkylphosphites with trichloroisocyanuric acid in acetonitrile and subsequent treatment with amines in presence KF-celite to give PB-1 and derivatives.

Novel and Efficient Synthesis of N,N-dialkylamino-O-alkyl-2-(1- methyl-2-oxopropylidene)phosphorohydrazido Oximes. Part 3

A novel and efficient method has been developed for the synthesis of N,N-dialkylamino-O-alkyl-2-(1-methyl-2-oxopropylidene)phosphorohydrazido oximes 5. The reactions involve the condensation of diacetylmonoxime and N,N-dialkylamino-O- alkylphosphorohydrazides in the presence of activated silica and give the corresponding target oximes in excellent yields under mild conditions.