The North Carolina Contribution to the CAPRISA 004 Study: The Global Health Initiative in Action

Cates, Willard; Kashuba, Angela D. M.

doi:10.18043/ncm.71.5.490

North Carolina Medical Journal

2010

DOI: 10.18043/ncm.71.5.490

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The North Carolina Contribution to the CAPRISA 004 Study: The Global Health Initiative in Action

Willard Cates¹,

Angela D. M. Kashuba²

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Rhodanine derivatives as potent anti-HIV and anti-HSV microbicides

et al. 2018

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Although highly active antiretroviral therapies (HAART) remarkably increased life expectancy of HIV positive people, the rate of novel HIV-1 infections worldwide still represent a major concern. In this context, pre-exposure prophylaxis (PrEP) approaches such as vaginal microbicide gels topically releasing antiretroviral drugs, showed to have a striking impact in limiting HIV-1 spread. Nevertheless, the co-presence of other genital infections, particularly those due to HSV-1 or 2, constitute a serious drawback that strongly limits the efficacy of PrEP approaches. For this reason, combinations of different compounds with mixed antiviral and antiretroviral activity are thoroughly investigated Here we report the synthesis and the biological evaluation of a novel series of rhodanine derivatives, which showed to inhibit both HIV-1 and HSV-1/2 replication at nanomolar concentration, and were found to be active also on acyclovir resistant HSV-2 strains. The compounds showed a considerable reduction of activity in presence of serum due to a high binding to serum albumin, as determined through in vitro ADME evaluations. However, the most promising compound of the series maintained a considerable activity in gel formulation, with an EC50 comparable to that obtained for the reference drug tenofovir. Moreover, the series of compounds showed pharmacokinetic properties suitable for topical formulation, thus suggesting that the novel rhodanine derivatives could represent effective agents to be used as dual anti HIV/HSV microbicides in PrEP approaches.

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Rhodanine derivatives as potent anti-HIV and anti-HSV microbicides

et al. 2018

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Understanding the Relevance of Global Health to North Carolina

Hawley

Fouché²,

Cates³

et al. 2010

North Carolina Medical Journal

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A round the world, countries and communities are addressing a diverse set of global health challenges. The range of global health problems include human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) and other infectious diseases, sexual and reproductive health, child health, chronic diseases, climate change, nutrition and food security, and health systems strengthening. Solutions to these profound global health issues, as well as their programmatic implementation, require the effective mobilization of science, technology, and interdisciplinary research.Funding for global health has increased substantially from all sources-government and private-over the past 10 years. Worldwide, health-related assistance from the Development Assistance Committee members of the Organization for Economic Cooperation and Development

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The North Carolina Contribution to the CAPRISA 004 Study: The Global Health Initiative in Action

Cited by 2 publications

References 2 publications

Rhodanine derivatives as potent anti-HIV and anti-HSV microbicides

Rhodanine derivatives as potent anti-HIV and anti-HSV microbicides

Understanding the Relevance of Global Health to North Carolina

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