Broad-spectrum Chemotherapeutic Properties Research Articles

A new erythrocyte-based biochemical approach to predict the antiproliferative effects of heterocyclic scaffolds: The case of indolone

BackgroundThe indole core is a key structural feature of many natural products and biomolecules with broad spectrum chemotherapeutic properties. Some of us have recently synthesized a library of biologically promising indolone-based compounds. The present study focuses on the effects of one of them, namely DPIT, on human erythrocytes. MethodsWe have examined the influence of DPIT on band 3 protein, intracellular ATP concentration and transport, caspase 3 activation, metabolic adaptation and membrane stability. ResultsOur study elucidates that DPIT, intercalated into the phospholipid bilayer, decreases the anion transport, the intracellular ATP concentration and the cytosolic pH, inducing a direct activation of caspase 3. ConclusionsStarting from the metabolic similarity between erythrocytes and cancer cells, we investigate how the metabolic derangements and membrane alterations induced by selected heterocycles could be related to the antiproliferative effects. General significanceOur work aims to propose a new model of study to predict the antiproliferative effects of heterocyclic scaffolds, pointing out that only one of the listed conditions would be unfavorable to the life cycle of neoplastic cells.

Synthesis, antibacterial and potential anti-HIV activity of some novel imidazole analogs

A series of 1-(2-methyl-4-nitro-imidazol-1-yl)-3-arylaminopropan-2-ones (2a-e), 2-methyl-5-nitro-1-{2-[arylmethoxy]ethyl}-1H-imidazoles (5a-d), and N-(3-hydroxyphenyl)-2-(substituted imidazol-1-yl)alkanamides (8a-e) were synthesized with the aim to develop novel imidazole analogs with broad-spectrum chemotherapeutic properties. Title compounds were evaluated for their anti-HIV and antibacterial activities.

Newer Aminopyrimidinimino Isatin Analogues as Non‐Nucleoside HIV‐1 Reverse Transcriptase Inhibitors for HIV and Other Opportunistic Infections of AIDS: Design, Synthesis and Biological Evaluation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Nevirapine derivatives with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS

A series of nevirapine derivatives has been synthesized in an effort to enhance the spectrum of chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. The nevirapine derivative bearing isoniazid moiety ( 3a) was found to be the most potent compound with EC 50 of < 0.0636 μM, CC 50 of > 1000 μM and selectivity index of > 15,723 which also exhibited 90% inhibition against Mycobacterium tuberculosis at 6.25 μg/ml. Compound 3c showed 100% inhibition against M. tuberculosis and also exhibited potent antibacterial activity against 24 pathogenic bacteria with MIC less than 1 μg/ml.

Synthesis of zidovudine prodrugs with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS

A series of prodrugs of zidovudine has been synthesized in an effort to enhance spectrum of chemotherapeutic properties for the effective treatment of HIV/AIDS. The 5′-OH function of zidovudine was esterified with ciprofloxacin, norfloxacin, isoniazide, pyrazinamide acetic acid. The anti-HIV-1 activity of the esters was determined in CEM cell-line and zidovudine ester bearing pyrazinamide acetic acid was found to be the most potent compound with EC 50 of < 0.0636 μM, CC 50 of > 1000 μM and selectivity index (SI) of > 15,723. Zidovudine prodrug bearing ciprofloxacin and norfloxacin moiety showed 100% inhibition against Mycobacterium tuberculosis H 37Rv at 6.25 μg/ml. The prodrugs were also found to exhibit antibacterial activity against 24 pathogenic bacteria. In vitro hydrolysis of the various esters in human plasma indicated that these agents were relatively stable toward plasma esterase with t 1/2 ranging from 20 to 240 min.

Synthesis, Antiviral and Antibacterial Activities of Isatin Mannich Bases

HIV is the most significant risk factor for many opportunistic infections like tuberculosis, hepatitis, bacterial infections etc. We designed an isatin lead compound as a novel non-nucleoside reverse transcriptase inhibitor with broad-spectrum chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. Compound 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[[N4-[3′-(4′-amino-5′-trimethoxybenzyl pyrimidin-2′-yl)imino-1′-(5-chloroisatinyl)[methyl]-N1-piperazinyl]-3-quinoline carboxylic acid (14) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV, HCV, M. tuberculosis and various pathogenic bacteria.

Newer aminopyrimidinimino isatin analogues as non-nucleoside HIV-1 reverse transcriptase inhibitors for HIV and other opportunistic infections of AIDS: design, synthesis and biological evaluation

Human immuno deficiency virus (HIV) weakens the immune system so that many opportunistic infections (OIs) like tuberculosis, hepatitis, bacterial infections etc can develop. In this paper, we designed aminopyrimidinimino isatin lead compound as a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with broad-spectrum chemotherapeutic properties for the effective treatment of AIDS and AIDS-related OIs. Compound 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[[N 4-[3'-(4'-amino-5'-trimethoxybenzyl pyrimidin-2'-yl)imino-1'-(5-methylisatinyl)]methyl]-N 1-piperazinyl]-3-quinoline carboxylic acid ( 10) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV, HCV, Mycobacterium tuberculosis and various pathogenic bacteria.

Aminopyrimidinimino Isatin Analogues: Design and Synthesis of Novel Non- Nucleoside HIV-1 Reverse Transcriptase Inhibitors with Broad- Spectrum Anti-Microbial Properties

HIV is the most significant risk factor for many opportunistic infections like tuberculosis, bacterial infections etc. In this paper, we designed aminopyrimidinimino isatin lead compound as a novel non-nucleoside reverse transcriptase inhibitor with broad-spectrum chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. Compound 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7[[N(4)-[3'-(4'-amino-5'-chloroben-zylpyrimidin-2'-yl)imino-1'-(5-methylisatinyl)] methyl]N(1)-piperazinyl]-3-quinoline carboxylic acid (10) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV-1 replication (EC(50): 9.4 microg /ml), M. tuberculosis (MIC: 3.13 microg /ml) and various pathogenic bacteria (MIC's: 1.22 microg /ml).

Design, synthesis and biological evaluation of novel non-nucleoside HIV-1 reverse transcriptase inhibitors with broad-spectrum chemotherapeutic properties

Acquired immunodeficiency syndrome (AIDS) results from infection by the retrovirus, human immunodeficiency virus (HIV). HIV is the most significant risk factor for many opportunistic infections like tuberculosis, hepatitis, bacterial infections, etc. In this paper, we designed aminopyrimidinimino isatin lead compound as a novel non-nucleoside reverse transcriptase inhibitor with broad-spectrum chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. Compound 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7[[ N 4-[3′-(4′-amino-5′-trimethoxybenzylpyrimidin-2′-yl)imino-1′-(5-fluoroisatinyl)]methyl]- N 1-piperazinyl]-3-quinoline carboxylic acid ( 12) emerged as the most potent broad-spectrum chemotherapeutic agent active against HIV, HCV, Mycobacterium tuberculosis and various pathogenic bacteria.

Synthesis of stavudine amino acid ester prodrugs with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS

A series of prodrugs of stavudine were synthesized in an effort to enhance spectrum of chemotherapeutic properties for the effective treatment of HIV/AIDS. The 5′-OH function of stavudine was esterified with ciprofloxacin, norfloxacin, isoniazide, pyrazinamide, piperazine and dimethylamine acetic acid. The anti-HIV-1 activity of the esters was determined in CEM cell line and stavudine ester bearing piperazine acetic acid was found to be the most potent compound with a selective index of >15,723. Stavudine prodrug bearing ciprofloxacin and norfloxacin acetic acid showed 100% inhibition against Mycobacterium tuberculosis H37Rv at 6.25 μg/mL. The prodrugs also exhibited antibacterial activity against 24 pathogenic bacteria. In vitro hydrolysis of the various esters in human plasma indicated that these agents were relatively stable toward plasma esterases with t1/2 ranging from 20–240 min.

Towards the design and development of agents with broad spectrum chemotherapeutic properties for the effective treatment of HIV / AIDS.

HIV is the most significant risk factor for many opportunistic infections like fungal, tuberculosis, etc. The intense media coverage of AIDS puts the public on an emotional roller caster, and inflated promises are engendered by each success. For the moment drugs acting as both HIV-reverse transcriptase inhibitors along with antimicrobial properties are one of the brightest hope. The Non-nucleoside reverse transcriptase inhibitors (NNRTIs) appear ideally suited for further development in the chemoprophylaxis and therapy of HIV infections. In recent years, isatinimino compounds have been reported to exhibit broad-spectrum chemotherapeutic properties that include anti-HIV, antituberculous, antifungal and antibacterial activities. Hence these leads should be regarded as structural hits in the search for more potent antimicrobial compounds with broad-spectrum chemotherapeutic properties for the effective treatment of HIV / AIDS. This review focuses on the design of isatinimino compounds, which resemble the NNRTIs for the development of an ideal anti-HIV drug.