Spirofused Tetrahydroisoquinoline-Oxindole Hybrids (Spiroquindolones) as Potential Multitarget Antimalarial Agents: Preliminary Hit Optimization and Efficacy Evaluation in Mice.

Previous studies suggest that 3',5'-dihydro-2'H-spiro[indoline-3,1'-isoquinolin]-2-ones (DSIIQs [spiroquindolones]) are multitarget antiplasmodial agents that combine the actions of spiroindolone and naphthylisoquinoline antimalarial agents. In this study, 12 analogues of compound (±)-5 (moxiquindole), the prototypical spiroquindolone, were synthesized and tested for antiplasmodial activity. Compound (±)-11 (a mixture of compounds 11a and 11b), the most potent analogue, displayed low-nanomolar activity against P.

Spirofused tetrahydroisoquinoline-oxindole hybrids as a novel class of fast acting antimalarial agents with multiple modes of action.

Molecular hybridization of privileged scaffolds may generate novel antiplasmodial chemotypes that display superior biological activity and delay drug resistance. In the present study, we describe the in vitro activities and mode of action of 3',4'-dihydro-2'H-spiro[indoline-3,1'-isoquinolin]-2-ones, a novel class of spirofused tetrahydroisoquinoline-oxindole hybrids, as novel antimalarial agents. Whole cell phenotypic screening of these compounds identified (14b), subsequently named (±)-moxiquindole, as the most potent compound in the current series with equipotent antiplasmodial activity against both chloroquine sensitive and multidrug resistant parasite strains with good selectivity.

Power dynamics as a determinant of access and utilization of nutrition services by pregnant and lactating adolescent girls in Trans-Mara East Sub-County, Narok County, Kenya.

Background: During pregnancy or lactating, adequate nutrition for adolescents becomes critical to reduce risks for both child and maternal-related morbidity and mortality. Power dynamics play a massive role in health outcomes. The main objective of this study was to examine the power dynamics in the families and communities and their impact on the pregnant and lactating adolescent girls' access and utilization of nutrition services in Trans-Mara East Sub-County, Narok County.

3',4'-Dihydro-2'H-spiro[indoline-3,1'-isoquinolin]-2-ones as potential anti-cancer agents: synthesis and preliminary screening.

Both tetrahydroisoquinolines (THIQs) and oxindoles (OXs) display a broad range of biological activities including anti-cancer activity, and are therefore recognized as two privileged scaffolds in drug discovery. In the present study, 24 3',4'-dihydro-2'H-spiro[indoline-3,1'-isoquinolin]-2-ones, designed as molecular hybrids of THIQ and OX, were synthesized and screened against 59 cell lines in the NCI-60 screen. Twenty compounds displayed weak to moderate inhibition of cell proliferation; among them, three compounds displayed at least 50% inhibition of cell proliferation.

Socio-demographic and facility-based determinants of perceived quality of nutrition Services of Pregnant and Lactating Adolescent Girls in Trans-Mara east Sub-County, Narok County, Kenya.

Background: It has been established that use and utilization of nutrition services among adolescents are highly linked to availability, access, cost and quality of care. The main objective of this study was to assess the socio-demographic and facility-based factors as proxies to access to perceived quality of nutrition-specific and nutrition-sensitive services among adolescents in Trans-Mara East Sub-County, Narok County.

Methods: The study adopted a cross-sectional approach that employed mixed methods on 291 households.