A series of pyrano[3,2 c]quinoline was evaluated for its in vivo efficacy as TNF-α inhibitor using LPS, phosphodiesterase (PDE)-4, and CIA assays in different mice/rat models. The synthesis was performed using one-pot multicomponent condensation between 2,4-dihydroxy-1-methylquinoline, malononitrile, and diverse un(substituted) aromatic aldehydes. In vivo efficacy of the title compounds was evaluated using LPS assay in BALB/c mice, PDE4 inhibition in ketamine-xylazine-induced anesthetize SD rats, and CIA assay was performed in DBA/1J mice as per the standard literature protocols. The outcome of the study revealed that compound 4v was found to be most promising candidate of the series. It was efficacious with 48.8 ± 13.0% inhibition of TNF-α release at 100 mg/kg p.o., in the LPS assay in Balb/c mice model. It was effective in PDE4 assay in ketamine-xylazine-induced anesthetize SD rats with duration of 38.3 ± 4.5 min for reversal of anesthetic effect and also showed significant inhibition of PDE4 in salbutamol treated U937 cell assay. It was also abolished TNF-α induced phosphorylation and degradation of IκBα. Ultimately, its effect on CIA-related bone and cartilage damage was found statistically similar to Enbrel.

BACKGROUND: The development and spread of antimalarial drug resistant parasites contributes to the global impact of the disease. In vivo efficacy assessments of treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. Artemisinin-based combinations have been adopted as the first-line treatment for uncomplicated P. falciparum malaria in Cameroon since 2004.
METHODS: A total of 177 children aged six-months to 10 years with uncomplicated mono-infected falciparum malaria were randomized (1:1) to receive artesunate/sulphadoxine-pyrimethamine (AS/SP) or artesunate/amodiaquine (AS/AQ) pediatric tablets and followed up for 28 days according to the standard World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response (ACPR) on day 28.
RESULTS: The PCR corrected cure rate was high, overall (88.1%, 95% CI 83.1-93.1), 85.9% (95% CI 78.2-93.6), and 90.2% (95% CI 83.8-96.6) for AS/SP and AS/AQ, respectively. Twenty-one treatment failures were observed during follow-up, constituting one (4.6%), 14 (8.2%), and six (3.5%) early treatment failure (ETF), late clinical failure (LCF), and late parasitological failure (LPF), respectively. The drugs were well tolerated with no serious adverse events.
CONCLUSIONS: Both AS/SP and AS/AQ are highly effective and well-tolerated treatments for uncomplicated P. falciparum malaria around the slope of Mount Cameroon.

BACKGROUND: The efficacy, tolerability and acceptability of a tea tree oil gel (200 mg/g) and face wash (7 mg/g) were evaluated for the treatment of mild to moderate facial acne.
METHODS: In this open-label, uncontrolled phase II pilot study, participants applied tea tree oil products to the face twice daily for 12 weeks and were assessed after 4, 8 and 12 weeks. Efficacy was determined from total numbers of facial acne lesions and the investigator global assessment (IGA) score. Tolerability was evaluated by the frequency of adverse events and the mean tolerability score determined at each visit. Product acceptability was assessed via a questionnaire at the end of the study period.
RESULTS: Altogether 18 participants were enrolled, of whom 14 completed the study. Mean total lesion counts were 23.7 at baseline, 17.2 at 4, 15.1 at 8 and 10.7 at 12 weeks. Total lesion counts differed significantly over time by repeated measures anova (P < 0.0001). The mean IGA score was 2.4 at baseline, 2.2 at 4, 2.0 at 8 and 1.9 at 12 weeks, which also differed significantly over time (P = 0.0094). No serious adverse events occurred and minor local tolerability events were limited to peeling, dryness and scaling, all of which resolved without intervention.
CONCLUSIONS: This study shows that the use of the tea tree oil products significantly improved mild to moderate acne and that the products were well tolerated.