Treatment of AIDS with Drugs Targeted to Inhibit Different Stages of the HIV Life Cycle

Sarin, Prem S.; Goldstein, Allan L.

doi:10.3109/08923979509019748

Cited by 7 publications

(11 citation statements)

References 64 publications

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“…However, 6-methyl DCK (10) was much less active (EC 50 ) 0.151 µM) and had a lower therapeutic index (218) than DCK. Similar results were observed with the four monomethoxy-substituted DCK isomers (3)(4)(5)(6). 5-Methoxy DCK (5) exhibited potent anti-HIV activity with an EC 50 value of 1.92 × 10 -4 µM and a TI value of 7.97 × 10 5 , which were slightly better than those of DCK.…”

Section: Resultssupporting

confidence: 76%

“…Most reactions were highly stereoselective (>88%). However, 13 was obtained with 6). When 1-adamantanecarbonyl chloride was the acylating agent, only the monoester 21 was obtained, probably due to the steric hindrance of the bulky substituent ortho to a hydroxyl group.…”

Section: Chemistrymentioning

confidence: 99%

“…Current understanding of molecular events in the HIV life cycle proposes seven steps: viral entry, reverse transcription, integration, gene expression, assembly, budding, and maturation. In theory, every stage in the viral life cycle could serve as a potential target for designing anti-HIV agents and therapies. , …”

Section: Introductionmentioning

confidence: 99%

“…In theory, every stage in the viral life cycle could serve as a potential target for designing anti-HIV agents and therapies. 5,6 Thirteen inhibitors of reverse transcriptase and protease have been approved by the FDA 7 and are currently used alone or as a part of a combination regimen to treat HIV infection in AIDS patients. These drugs can effectively suppress HIV replication, thus delaying disease progress and prolonging patients' survival.…”

Section: Introductionmentioning

confidence: 99%

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Anti-AIDS Agents. 37. Synthesis and Structure−Activity Relationships of (3‘R,4‘R)-(+)-cis-Khellactone Derivatives as Novel Potent Anti-HIV Agents

et al. 1999

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To explore the structural requirements of (+)-cis-khellactone derivatives as novel anti-HIV agents, 24 monosubstituted 3', 4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) derivatives were synthesized asymmetrically. These compounds included 4 isomeric monomethoxy analogues (3-6), 4 isomeric monomethyl analogues (7-10), 4 4-alkyl/aryl-substituted analogues (11-14), and 12 4-methyl-(+)-cis-khellactone derivatives (15-26) with varying 3', 4'-substituents. These (+)-cis-khellactone derivatives were screened against HIV-1 replication in acutely infected H9 lymphocytes. The results demonstrated that the (3'R,4'R)-(+)-cis-khellactone skeleton, two (S)-(-)-camphanoyl groups at the 3'- and 4'-positions, and a methyl group on the coumarin ring, except at the 6-position, were optimal structural moieties for anti-HIV activity. 3-Methyl- (7), 4-methyl- (8), and 5-methyl- (9) 3',4'-di-O-(S)-camphanoyl-(3'R, 4'R)-(+)-cis-khellactone showed EC(50) and therapeutic index values of <5.25 x 10(-5) microM and >2.15 x 10(6), respectively, in H9 lymphocytes, which are much better than those of DCK and AZT in the same assay. Furthermore, 8 and 9 also showed potent inhibitory activity against HIV-1 replication in the CEM-SS cell line, and most monosubstituted DCK analogues were less toxic than DCK in both assays.

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Section: Resultssupporting

confidence: 76%

Section: Chemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Anti-AIDS Agents. 37. Synthesis and Structure−Activity Relationships of (3‘R,4‘R)-(+)-cis-Khellactone Derivatives as Novel Potent Anti-HIV Agents

et al. 1999

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“…In this regard, it is noteworthy that several cancer and HIV medicines that have been the source of initial excitement have subsequently failed to live up to their promise – even for people in desperate situations. These include, for example, cytokines for renal carcinoma, anti‐angiogenic therapies for breast cancer and some earlier anti‐retroviral drugs used in the treatment of AIDS . In the context of life‐threatening illness, we also need to bear in mind that effective palliation may be foregone if patients are led to believe that an expensive new treatment is their ‘only hope’.…”

Section: Ethical Considerations and Tensions In The Provision Of Compmentioning

confidence: 99%

Dilemmas in the compassionate supply of investigational cancer drugs

Lewis

Lipworth

Kerridge

et al. 2014

Internal Medicine Journal

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In Australia, patients who want to access medicines that are not yet approved have only two options: to enrol in a clinical trial if they are eligible, or obtain their medicine through 'compassionate supply', which is provided at the discretion of the manufacturer. In this article, we explore ethical issues associated with the provision of oncology medicines that are still in development, either prior to regulatory approval or government reimbursement.

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Drug discovery: Past, present and future

Kaul

1998

Progress in Drug Research

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Treatment of AIDS with Drugs Targeted to Inhibit Different Stages of the HIV Life Cycle

Cited by 7 publications

References 64 publications

Anti-AIDS Agents. 37. Synthesis and Structure−Activity Relationships of (3‘R,4‘R)-(+)-cis-Khellactone Derivatives as Novel Potent Anti-HIV Agents

Anti-AIDS Agents. 37. Synthesis and Structure−Activity Relationships of (3‘R,4‘R)-(+)-cis-Khellactone Derivatives as Novel Potent Anti-HIV Agents

Dilemmas in the compassionate supply of investigational cancer drugs

Drug discovery: Past, present and future

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