Diksha Katiyar

Synthesis and antimycobacterial activity of 3,5-disubstituted thiadiazine thiones☆

A series of 3,5-disubstituted thiadiazine thiones (4-24) have been synthesized by reaction of primary amines with carbon disulphide followed by cyclocondensation of the resulting intermediate with formaldehyde and primary amines or amino acids. The compounds were screened for antitubercular activity in vitro against Mycobacterium tuberculosis H37Rv. Three compounds 4, 12 and 18 showed antimycobacterial activity with MIC 12.5 microg/mL. Compound 4, was tested in vitro against five multidrug resistant (MDR) strains of M. tuberculosis and was found to be active. Compound 4 also exhibited activity in vivo. While all the mice died in the untreated group, the mean survival time (MST) of the compound treated mice was enhanced, 33% mice were surviving in treated group and the load of bacilli in the lung was considerably less in the compound treated group than in the untreated control group.

Recent Developments in Search of Antifilarial Agents

Filariasis, caused by spirunid nematodes, is one of the most prevalent diseases of tropical and subtropical countries and encompasses a number of different pathological conditions. It has great impact on the socioeconomic conditions of the people affected with this disease. The most common type of filariasis is a lymphatic filariasis caused by a parasite that lives in human lymph system. Like malaria, it is also caused by mosquito bites. The life cycle of the parasite, pathogenesis and diagnosis of filariasis have been briefly reviewed here in. Different strategies to control this disease have been discussed with major emphasis on the mechanisms, merits and demerits of the existing drugs and the drugs under pipeline. New antifilarial prototypes discovered recently and finally the future perspective to control the disease have also been elucidated.

Amberlite IR-120 catalysed efficient synthesis of glycosyl enamines and their application

β-Keto esters and acetyl acetone on condensation with glycosylated amino esters in the presence of IR-120 resin resulted in high yields of glycosyl enamino esters or ketones. The latter on cyclisation with NaH in toluene at reflux gave 6-glycosyl-5,6-dihydro-1H-pyridin-4-ones in fair to good yields.

Diastereoselective Synthesis of Galactopyranosyl Amino Esters and Their Transformation into C‐Nucleosides

Abstract Galactopyranosylated olefinic ester (4) on conjugate addition of amines yielded stereoselectively galactopyranosylated amino esters (5–18) in fair to good yield. The selected amino esters (5, 6, 13, and 15–17) on reaction with isocyanates resulted in ureido galactopyranosyl amino esters (19–24) in very good yields. Lactamization of compounds 19–24 with DBU, 4 Å MS, and tetrabutylammonium bromide in refluxing toluene gave respective C‐galactopyranosyl dihydropyrimidine‐2,4‐diones (25–30) in respectable yields.

INHIBITORS OF FILARIAL GAMMA-GLUTAMYL CYCLE ENZYMES AS POSSIBLE MACROFILARICIDAL AGENTS

The sensitivity of two γ-glutamyl cycle enzymes i.e. glutamate cysteine ligase (GCL) and γ-glutamyl transpeptidase (γ-GT) from bovine filarial worms Setaria cervi and their counterparts from mammalian liver to known inhibitors i.e. buthionine sulfoximine vs. GCL and serine-borate vs. γ-GT were compared. Two chemical classes i.e. diglycosylated diaminoalkanes (DGDA) and coumarins were studied for their inhibition against filarial GCL, glutathione synthetase (GS) and γ-GT and the most effective inhibitors of filarial enzymes were also looked for their effect on GSH levels of bovine filariae S. cervi in vitro. Results revealed some definite correlation between the enzyme inhibition with GSH depletion in S. cervi females by certain DGDA and coumarin derivatives.

A VERSATILE SYNTHESIS OF DIHYDROPYRIMIDINONE C-NUCLEOSIDES +

A versatile synthesis of N‐substituted dihydropyrimidinone C‐nucleosides (20–29) is described. Glycosyl amino esters (3–9), obtained by reductive alkylation of glycosyl amino esters 1 and 2, on condensation with different isocyanates afforded respective ureido derivatives (10–19) in good to quantitative yields. The latter on cyclative amidation with a combination of DBU/TBAB (tetrabutylammonium bromide)/4Å molecular sieve gave the corresponding nucleosides (20–29) in good yields.