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Biomedical subjects

A Q Siddiqui

Publications and source records attributed to A Q Siddiqui.

14 recordsLinked to original sources
PubMed1999

Design and synthesis of lipophilic phosphoramidate d4T-MP prodrugs expressing high potency against HIV in cell culture: structural determinants for in vitro activity and QSAR.

A series of new substituted-aryl phosphoramidate derivatives of the anti-HIV drug d4T were synthesized as membrane-soluble nucleotide prodrugs, to extend and quantify the SAR observed for an earlier series of related derivatives. All of the compounds were found to be significantly more potent against HIV in cell culture than the nucleoside analogue d4T, and most were also found to be significantly more potent than the parent phosphoramidate. A Hansch type QSAR analysis was applied to the combined series of 21 compounds. The results of this analysis revealed anti-HIV activity to be principally dependent on lipophilicity in a quadratic manner, with terms representing substituent steric bulk and electronic effects having a minimal significance.

Amides↗
PubMed1999

Simple mono-derivatisation of the aryl moiety of D4A and DDA-based phosphoramidate prodrugs significantly enhances their anti-HIV potency in cell culture.

Simple mono-derivatisation of the aryl moiety of some phosphoramidate pronucleotide derivatives of d4A and ddA served to increase the lipophilicity of these membrane-soluble prodrugs. A concomitant and significant enhancement of potency against HIV-1 and HIV-2 in vitro was observed for the ddA- and d4A-based prodrugs compared to the original underivatised prodrugs.

Anti-HIV Agents↗
PubMed1999

The presence of substituents on the aryl moiety of the aryl phosphoramidate derivative of d4T enhances anti-HIV efficacy in cell culture: A structure-activity relationship.

New substituted-aryl phosphoramidate derivatives of the anti-HIV drug d4T were synthesized as membrane-soluble intracellular prodrugs for the free bioactive phosphate to establish relationship(s) between compound structure and in vitro antiviral activity. The majority of compounds demonstrated an elevation of in vitro potency relative to that of the parent nucleoside, and unlike d4T, all retained full activity in thymidine kinase-deficient cells. The compound bearing a p-chloro aryl group (8e) expressed nanomolar activity in vitro, a 14-fold increase in activity relative to that of the unsubstituted phosphoramidate (100-fold compared to d4T). An assay using pig liver esterase was used to establish the stability of the compounds to enzymatic degradation. While there was no apparent correlation between in vitro activity and half-life of enzymatic degradation, there was a close correlation between compound lipophilicity, determined by octanol/water partition coefficient, and in vitro potency. We suggest that substitutions made to the aryl moiety of the aryl phosphoramidate of d4T that result in enhancing lipophilicity may serve to increase the cellular uptake of the prodrug by passive diffusion, leading to the expression of antiviral potency at reduced prodrug concentrations.

3T3 Cells↗
PubMed1980

Age and mortality trends in residents of an institution for the mentally handicapped.

Ten years' statistics of age and mortality trends in a large institution are reported. It is shown that the residents are still an ageing population and that the higher mortality of the mentally handicapped is largely due to deaths from respiratory causes, as previously reported. Down syndrome is separately analysed and shows a sharp rise in mortality at a considerably earlier age than other mentally handicapped residents.

Adolescent↗
PubMed1979

The hematology of mrigal, Cirrhina mrigala (Ham.) (Teleostei: Cyprinidae).

Hematological parameters of a carp, Cirrhina mrigala, are reported here. Haematocrit ranged from 29.0 to 44.0%. The range of hemoglobin was 7.06 to 11.86 g/100 ml of blood, and the total number of erythrocytes varied from 1.7 to 3.0 million/mm3 of the blood, both hemoglobin and erythrocyte concentrations being higher in males than in the females. Mean ESR was 1.88 mm/h, with higher ESR in females (2.05 mm/h) than in the males (1.67 mm/h). The clotting time in males (41.0 seconds) was lower than in the females (63.5 seconds). Hematological values varied with the size and weight of the fishes. Variations in hematological parameters with season and in fishes of different maturation states were quite apparent.

Aging↗