Ricerc@Sapienza

Due to the biological liability of diketo acid (DKA) chain, we transferred this element of our previously reported anti-HIV-1 pyrrolyl derivatives to a non-DKA scaffold, obtaining a series of pyrrolyl-pyrazole carboxylic acids as new RNase H inhibitors. Among the newly synthesized derivatives, oxyphenylpyrrolyl-pyrazoles demonstrated inhibitory activities within the low micromolar/submicromolar range with compound 11b being the most potent. Interestingly, all tested compounds showed up to 2 orders of magnitude of selectivity for RNase H vs integrase.

INTRODUCTION The gastrointestinal tract is a major site of HIV localization and even
though cART (combined AntiRetroviral Therapy) leads to suppression of HIV replication
the gastrointestinal pathology is still persistent. In these patients increased levels of inflammation
and decreased levels of mucosal repair and regeneration are observed. Consequently
novel directions for dietary and therapeutic interventions that restore the immunological
and epithelial integrity of the mucosal barrier are needed. Since HIV infected patients host

Abstract
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Introduction:

Following recent attention focused on IL-32 as an important component involved in the inflammatory cytokine network, we speculated that IL-32's action on IFN-γ and IFN-γ secreting T cell subsets may help sustain the immune activation and dysregulation found in patients with HIV-1 achieving viral suppression. To explore this hypothesis, transcript levels of IL-32 and IFN-γ were evaluated in PBMC from 139 virologically suppressed HIV-1-infected patients and from 63 healthy individuals by Real Time RT-PCR assays.