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Biomedical subjects

N Mahmood

Publications and source records attributed to N Mahmood.

At least 37 records · Page 2Linked to original sources
PubMed1996

Constituents of Ardisia japonica and their in vitro anti-HIV activity.

As part of our screening of anti-AIDS agents from medicinal plants, the MeOH extract of the aerial parts of Ardisia japonica was tested, and it showed moderate in vitro anti-HIV activity. Reexamination to identify the compounds responsible for the anti-HIV activity revealed several known compounds and a new triterpenoid saponin (4) whose structure elucidation was accomplished by 1H-1H correlation spectroscopy (COSY, HOHAHA, ROESY) and 1H-13C heteronuclear correlation (HETCOR) NMR experiments. All of the isolated compounds were tested and, although none of the triterpenoid saponins was active, bergenin and norbergenin showed weak anti-HIV activity.

Antiviral Agents↗
PubMed1995

Synthesis and biological evaluation of N6-cycloalkyl derivatives of 1-deazaadenine nucleosides: a new class of anti-human immunodeficiency virus agents.

A series of 1-deazaadenine nucleosides with the N6 nitrogen unsubstituted or bearing methyl or cycloalkyl substituents, with or without a chloro group in the 2-position, and with the glycosylic moiety being ribose (1-16), 2'-deoxyribose (17-32), or 2', 3'-dideoxyribose (33-48) were designed and synthesized starting from 5,7-dichloro-3H-imidazo[4,5-b] pyridine (50). These compounds were evaluated for their in vitro activity against human immunodeficiency virus type-1 (HIV-1) and herpes simplex virus type-1 (HSV-1). In addition they were tested for their ability to inhibit adenosine deaminase (ADA) from calf intestine. While the parent compounds 1-deazaadenosine (9), 2'-deoxy-1-deazaadenosine (25), and 2',3'-dideoxy-1- deazaadenosine (41) and the corresponding 2-chloro derivatives were inactive, nucleosides bearing cycloalkyl substituents on N6 exhibited moderate to good anti-HIV-1 activity, compared to 2',3'-dideoxyadenosine, with the degree and pattern of improvement depending on the structure of the sugar moiety. In general, 2'-deoxy- and 2',3'-dideoxy derivatives were more potent compounds than the corresponding ribose nucleosides. Compounds bearing a 6-cycloheptyl or cyclooctylamine were the most active in every series. The presence of a chloro group in the 2-position improved both activity and therapeutic index in every series, the most active compound being 2'-deoxy-2-chloro-N6-cycloheptyl-1-deazaadenosine (23; ED50 = 0.2 microM). On the other hand, most of these derivatives were inactive as anti-HSV-1 agents, showing a high degree of virus selectivity. The 1-deazaadenine derivatives were not substrates of adenosine deaminase, and some of them proved to be good inhibitors of the enzyme. However, the ADA inhibitory activity does not account for the antiviral potency since increased lipophilicity and steric hindrance of substituents resulted in derivatives much less active than the parent compounds.

Adenosine↗
PubMed1995

Anti-(human immunodeficiency virus) activity of polyoxotungstates and their inhibition of human immunodeficiency virus reverse transcriptase.

Heteropolyoxotungstates of the Keggin class containing different heteroatoms were tested for inhibition of two strains of human immunodeficiency virus 1 (HIV-1); they exhibited varying antiviral activity. Compounds containing boron were inactive, only one of those containing phosphorus showed selective anti-viral activity, whereas all silicon-containing compounds exhibited significant anti-viral activity in C8166 cells infected with the IIIB strain. Their effectiveness was some 10-fold higher in JM cells with selectivity indices of about 2000. The silicotungstates were effective inhibitors of HIV reverse transcriptase, showing greater inhibition with RNA/DNA template primers than with DNA/DNA template.primer. Kinetic analysis demonstrated that they inhibit the enzyme by different mechanisms, as, of the four compounds examined, two competed with template.primer and two competed with deoxynucleoside triphosphate. Inhibition of DNA polymerase activity by these compounds was compared using polymerases from different sources, including human; although not necessarily most specific for HIV-1 reverse transcriptase, they did not inhibit all DNA polymerases to a similar degree.

Antiviral Agents↗
PubMed1995

Augmentation of chrysotile-induced oxidative stress by BHA in mice lungs.

Asbestos is known to induce oxidative stress in the lung. The consumption of butylated hydroxyanisole (BHA) in preserved food and soft drinks is increasing in the general population, which includes workers in asbestos factories. Because there is no information on the effect of co-exposure to chrysotile and BHA, the time-dependent effects of a single intratracheal dose of chrysotile (1 mg per mouse) and a single ip dose of BHA (350 mg/kg body weight) on various indices of oxidative stress such as lipid peroxidation, hydrogen peroxide generation, glutathione peroxidase (GPX), glutathione reductase (GR), catalase, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione (GSH) were followed for up to 14 days. Microsomal lipid peroxidation (as well as that induced by NADPH) was significantly enhanced by BHA in the chrysotile-exposed group. GPX and GR activities in the same group were gradually decreased by BHA. Non-significant modulation of catalase activity by BHA was also noted. BHA induces GSH to a significant extent in lungs exposed with chrysotile. An increase in the G6PDH activity was maximal (19%; P < 0.05) at day 3. The results clearly demonstrate that BHA enhances chrysotile-induced oxidative stress in the lung.

Animals↗
PubMed1994

Certain phosphoramidate derivatives of dideoxy uridine (ddU) are active against HIV and successfully by-pass thymidine kinase.

As part of our effort to deliver masked phosphates inside living cells we have discovered that certain phosphate triester derivatives of the inactive nucleoside analogue, dideoxy uridine (ddU) are inhibitors of HIV replication at microM levels. Moreover, we note that certain phosphoramidate derivatives retain their activity in thymidine kinase-deficient cells, which indicates that they do indeed act by intracellular release of the free nucleotide, and that they successfully by-pass the nucleoside kinase. The increased structural freedom in drug design which this allows may have implications for dealing with the emergence of resistance and may stimulate the discovery of improved therapeutic agents.

Antiviral Agents↗
PubMed1994

Anti-HIV-1 activity of chemically modified heparins: correlation between binding to the V3 loop of gp120 and inhibition of cellular HIV-1 infection in vitro.

Chemically modified heparins were tested for their activities in (i) inhibiting HIV-1 replication in vitro and (ii) inhibiting the binding to recombinant HIV-1 gp120 of monoclonal antibodies specific for the V3 loop. The results reveal that N-desulfation reduces activity, although this is largely restored on N-acetylation. Selective O-desulfation also markedly reduces activity, whereas carboxyl reduction has little effect. Overall these results show that the anti-HIV-1 activity of heparin does not depend simply on negative density, and indicate instead that particular structures, notably O-sulfates, are involved. Our studies reveal that for chemically modified heparins and heparin-derived fragments there is a striking correlation between anti-HIV-1 activity in vitro and binding to the V3 loop of gp120 in solid phase ELISA. This strongly suggests that the heparin exerts its anti-HIV-1 activity by binding to the V3 loop of gp120.

Acetylation↗
PubMed1994

Differential role of hydrogen peroxide and organic peroxides in augmenting asbestos-mediated DNA damage: implications for asbestos induced carcinogenesis.

The incubation of asbestos with DNA in presence of peroxides augmented DNA damage several fold as compared to the damage caused by individual treatments. Asbestos in presence of hydrogen peroxide causes DNA double strand breaks, damage to its deoxyribose sugar moiety and enhanced DNA fidelity. However, only DNA double strand breaks and enhanced DNA fidelity could be recorded in presence of organic hydroperoxide/peroxide but no DNA sugar damage could be observed. Further, the extent of DNA damage could be correlated to the carcinogenic potential of asbestos fibre. Crocidolite, the most carcinogenic variety of asbestos, produces maximum damage to DNA in presence of both hydrogen peroxide and organic hydroperoxide/peroxide while chrysolite which is only a co-carcinogen produces significantly less DNA damage. The observed differences in DNA damage by hydrogen peroxide and organic hydroperoxide/peroxide have been ascribed to the differential reactivity of DNA with hydroxyl and alkoxy/aryloxy free radicals produced respectively from these inorganic and organic peroxides.

Animals↗
PubMed1994

Antiviral activity of natural and semi-synthetic chromone alkaloids.

The activity against human immunodeficiency virus (HIV) and herpes simplex virus (HSV), of the non-polar fraction of a methanolic extract of the rootbark of Schumanniophyton magnificum was found to be present in a fraction containing the chromone secondary amine schumannificine 1. Other chromone alkaloids present in the plant were isolated and tested for inhibition of HIV and HSV infections in C8166 and Vero cells, respectively. Acyl and methyl derivatives were prepared and tested. Of all the compounds tested, schumannificine 1 displayed the greatest activity against HIV, whereas potent anti-HSV activity was observed for a number of its derivatives. The presence of a piperidine ring and unsubstituted hydroxy groups on the molecules seems to favour the anti-HIV activity. The anti-HIV activity is considered to be due to irreversible binding to gp120 rather than inhibition of reverse transcriptase or protease.

Alkaloids↗
PubMed1994

Synthesis and anti-HIV activity of some novel diaryl phosphate derivatives of AZT.

Novel diaryl phosphate triester derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials were designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In particular, novel parasubstituted diaryl phosphate derivatives were prepared. In vitro evaluation revealed the compounds to have a pronounced and selective antiviral effect, the magnitude of which varied considerably with the nature of the aryl substituent. In particular, strongly electron-withdrawing aryl substituents correlate with high anti-HIV potency in C8166 cells. Along with AZT, the compounds are poorly effective in JM cells, which appear to lack thymidine kinase, indicating the phosphates to act as pro-drugs of the nucleoside rather than of the free phosphate.

Animals↗
PubMed1994

Constituents of Werneria ciliolata and their in vitro anti-HIV activity.

The aerial part of Werneria ciliolata afforded a series of new diterpenes: two ent-kaurane derivatives, a norkaurane, an ent-manoyloxide derivative, a dimeric diterpene, as well as a rare diterpene. Their structures were elucidated by spectroscopic methods, including the concerted application of 1D NMR techniques (DEPT and NOEDS) and 2D NMR techniques (1H-1H COSY and HETCOR). In addition, four known kauranes, four coumarins and 6-hydroxytremetone were isolated. All isolated compounds from W. ciliolata and W. dactylophylla were tested in vitro for anti-viral activity against HIV-1, but only 6-hydroxytremetone showed a significant anti-HIV-1 activity.

Antiviral Agents↗
PubMed1994

The role of soda lime during administration of inhaled nitric oxide.

We have studied the ability of three commercially available preparations of soda lime to act as nitrogen dioxide scavengers during administration of inhaled nitric oxide. Soda lime, with a green to brown colour change (indicator = potassium permanganate), markedly reduced concentrations of nitrogen dioxide, but also markedly reduced inhaled concentrations of nitric oxide. The other varieties of soda lime, with colour changes from pink to white (indicator = kenazol yellow) or white to violet (indicator = ethyl violet), produced little effect on concentrations of nitrogen dioxide. None of the above soda limes can be recommended for use as a nitrogen dioxide scavenger during administration of inhaled nitric oxide.

Calcium Compounds↗
PubMed1994

Early studies on a candidate intracellular subunit vaccine NFU.Ac.HIV[JM] for prevention and/or modification of HIV-related disease.

A candidate HIV subunit vaccine NFU.Ac.HIV[JM] was prepared by detergent and formaldehyde treatment of HIV-infected JM cells. The preparation contained HIV polypeptides at 200, 118, 70, 41 and 24 kD, with reactivity by immunoblotting of approximately fifteen virus-specific polypeptides including polypeptides at 119, 55, 41 and 24 kD, which may represent gp 120, p55, gp41 and p24, respectively. The content of gp120 was estimated to be 5 micrograms/ml. The vaccine was immunogenic in a rabbit, inducing neutralising antibody and reactivity by ELISA and by immunoblotting against a number of HIV polypeptides including those of molecular weights 24, 41, 55 nd 120 kD. The vaccine contained no infectious HIV or reverse transcriptase enzyme activity.

AIDS Vaccines↗
PubMed1994

Effect of coexposure to asbestos and kerosene soot on pulmonary drug-metabolizing enzyme system.

This article reports the effect of coexposure to Indian chrysotile asbestos (5 mg/rat) and kerosene soot (5 mg/rat) on the pulmonary phase I and phase II drug-metabolizing enzymes 1, 4, 8, 16, 30, 90, and 150 days after a single intratracheal inoculation. Exposure to soot resulted in a significant induction of the pulmonary microsomal cytochrome P450 and the activity of dependent monooxygenase, benzo(a)pyrene (B[a]P) hydroxylase, and epoxide hydrase at all time intervals. On the other hand, the cytosolic glutathione S-transferase (GST) activity was induced at days 1, 4, 8, 16, and 30 after exposure, followed by inhibition in the enzyme activity. In contrast, chrysotile exposure depleted cytochrome P450, B[a]P hydroxylase, epoxide hydrase, and GST at initial stages, while all these parameters except GST were induced at later stages. However, coexposure to chrysotile and soot led to a significant inhibition in the cytochrome P450 levels, activities of B[a]P hydroxylase, epoxide hydrase, and GST at initial stages of exposure. At advanced stages, however, an additional increase in cytochrome P450, B[a]P hydroxylase, and epoxide hydrase but a decrease in GST was observed. These results clearly show that the intratracheal coexposure to high levels of asbestos and kerosene soot alters the metabolic activity of the lung, which is turn may retain toxins in the system for a longer period, resulting in adverse pathological disorders.

Animals↗
PubMed1993

Inhibition of HIV infection by flavanoids.

Of a variety of flavanoids, the flavans were generally more effective than flavones and flavanones in selective inhibition of HIV-1, HIV-2 or SIV infection. Studies of their effects on the binding of sCD4 and antibody to gp120 indicated that the effective compounds interact irreversibly with gp120 to inactive virus infectivity and block infection.

CD4 Antigens↗