32 research outputs found

    New pyrrole derivatives with potent tubulin polymerization inhibiting activity as anticancer agents including hedgehog-dependent cancer

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    We synthesized 3-aroyl-1-arylpyrrole (ARAP) derivatives as potential anticancer agents having different substituents at the pendant 1-phenyl ring. Both the 1-phenyl ring and 3-(3,4,5-trimethoxyphenyl)carbonyl moieties were mandatory to achieve potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARAP 22 showed strong inhibition of the P-glycoprotein-overexpressing NCI-ADR-RES and Messa/Dx5MDR cell lines. Compounds 22 and 27 suppressed in vitro the Hedgehog signaling pathway, strongly reducing luciferase activity in SAG treated NIH3T3 Shh-Light II cells, and inhibited the growth of medulloblastoma D283 cells at nanomolar concentrations. ARAPs 22 and 27 represent a new potent class of tubulin polymerization and cancer cell growth inhibitors with the potential to inhibit the Hedgehog signaling pathway

    Entomological risk of African tick-bite fever (Rickettsia africae infection) in Eswatini.

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    BackgroundRickettsia africae is a tick-borne bacterium that causes African tick-bite fever (ATBF) in humans. In southern Africa, the tick Amblyomma hebraeum serves as the primary vector and reservoir for R. africae and transmits the bacterium during any life stage. Previous research has shown that even when malaria has been dramatically reduced, unexplained acute febrile illnesses persist and may be explained by the serological evidence of rickettsiae in humans.Methodology/principal findingsWe collected 12,711 questing Amblyomma larvae across multiple land use types in a savanna landscape in Eswatini. Our results show that host-seeking Amblyomma larvae are abundant across both space and time, with no significant difference in density by land use or season. We investigated the entomological risk (density of infected larvae) of ATBF from A. hebraeum larvae by testing over 1,600 individual larvae for the presence of R. africae using a novel multiplex qPCR assay. We found an infection prevalence of 64.9% (95% CI: 62.1-67.6%) with no land use type significantly impacting prevalence during the dry season of 2018. The mean density of infected larvae was 57.3 individuals per 100m2 (95% CI: 49-65 individuals per 100m2).ConclusionsCollectively, our results demonstrate R. africae infected A. hebraeum larvae, the most common tick species and life stage to bite humans in southern Africa, are ubiquitous in the savanna landscape of this region. Increased awareness of rickettsial diseases is warranted for policymakers, scientists, clinicians, and patients. Early detection of disease via increased clinician awareness and rapid diagnostics will improve patient outcomes for travelers and residents of this region
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