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Biomedical subjects

R A Sharma

Publications and source records attributed to R A Sharma.

52 records · Page 3Linked to original sources

Antiviral action and cellular toxicity of four thymidine analogues: 5-ethyl-,5-vinyl-, 5-propyl-, and 5-allyl-2'- deoxyuridine.

5-Ethyl-, 5-vinyl-, 5-propyl-, and 5-allyl-2'-deoxyuridine (dUrd) had antiviral activity against herpes simplex type 1 and type 2 grown in HeLa TK(-) cells, in the order 5-vinyl-dUrd, 5-ethyl-dUrd, 5-propyl-dUrd, 5-allyl-dUrd, but they were inactive against a TK(-) mutant of herpes simplex type 1. The antiviral activity of these compounds could be partially reversed by thymidine. Except for 5-vinyl-dUrd, they were not toxic to WI-38 and HeLa TK(-) cells at a concentration of 25 muM. All four analogues inhibited the growth of herpes simplex type 1-transformed HeLa TK(-) cells at a concentration of 1 muM.

Antineoplastic Agents↗

Synthesis and biological activity of 4-beta-Iribofuranosyl-1,3-dihydroxybenzene ("1,3-dideazauridine").

In view of the marked antitumor activity of 3-deazauridine, the synthesis of 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene (1,3-dideazauridine) and its dibenzyl derivative was carried out. 4-Bromo-1,3-dihydroxybenzene was converted to its dibenzyl derivative, which, upon reaction with n-butyllithium followed by treatment with anhydrous cadmium chloride, gave bis(1,3-dibenzyloxyphenyl-4)cadmium. Condensation of this intermediate with 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride in refluxing toluene, and subsequent removal of the protecting benzoyl groups, afforded 4-(beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene which, upon catalytic hydrogenation over Pd/C, furnished the desired 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene. The beta configuration at the anomeric center was established by NMR and hydrogen bonding studies. 4-(Beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene inhibited the growth of leukemia L1210 cells by 50% at 7 x 10(-6) M, and that of mammary carcinoma TA3 cells at 5 x 10(-5) M. Dideazauridine itself was less active, inhibiting the leukemia L1210 but not the TA3 cells at 1 x 10(-4) M, but the compound was significantly active against herpes simplex (type I) virus in vitro.

3-Deazauridine↗

Preparation and biological activity of some aminoacyl and peptidyl derivatives of 2'-amino-2'-deoxyuridine.

Several aminoacyl and peptidyl derivatives of 2'-amino-2'-deoxyuridine have been synthesized. 2'-Amino-2'-deoxyuridine (I) and 2'-N-glycyl-2'-amino-2'-deoxyuridine (IIIa) were condensed with N-Cbz blocked p-nitrophenyl esters of the appropriate amino acids to afford the protected aminoacyl and peptidyl nucleosides. Removal of the protecting groups gave the title compounds in good yields. The biological effects of these derivatives are discussed.

Deoxyuridine↗

Acquired pure red cell aplasia in a child.

Primary acquired pure red cell aplasia is a rare occurrence in childhood. An eleven-year old boy presented to us with pallor, which required multiple packed red cell transfusions. He did not have hepatosplenomegaly, jaundice or lymphadenopathy. Bone marrow examination revealed the diagnosis of pure red cell aplasia. All possible investigations were done to exclude secondary causes of pure red cell aplasia. No secondary cause was found on investigations. Rheumatoid factor and anti-nuclear antibodies were positive. He was started on oral steroids, to which he did not respond. He was then given cyclosporine A. Response to cyclosporine was dramatic and the child now does not require any transfusions.

Blood Transfusion↗