Antimalarials and macrolides: a review of off-label pharmacotherapies during the first wave of the SARS-CoV-2 pandemic

Abstract We critically analyzed clinical trials performed with chloroquine (CQ) and hydroxychloroquine (HCQ) with or without macrolides during the first wave of COVID-19 and discussed the design and limitations of peer-reviewed studies from January to July 2020. Seventeen studies were eligible for the discussion. CQ and HCQ did not demonstrate clinical advantages that justified their inclusion in therapeutic regimens of free prescription for treatment or prophylactic purposes, as suggested by health authorities, including in Brazil, during the first wave. Around August 2020, robust data had already indicated that pharmacological effects of CQ, HCQ and macrolides as anti-SARS-CoV-2 molecules were limited to in vitro conditions and largely based on retrospective trials with low quality and weak internal validity, which made evidence superficial for decision-making. Up to that point, most randomized and nonrandomized clinical trials did not reveal beneficial effects of CQ or HCQ with or without macrolides to reduce lethality, rate of intubation, days of hospitalization, respiratory support/mechanical ventilation requirements, duration, type and number of symptoms, and death and were unsuccessful in increasing virus elimination and/or days alive in hospitalized or ambulatory patients with COVID-19. In addition, many studies have demonstrated that side effects are more common in CQ-or HCQ-treated patients.

Chemical composition, larvicidal and cytotoxic activity of Annona salzmannii (Annonaceae) seed oil

The seed oil of Annona salzmannii A. DC. was analyzed by GC-MS and 1H qNMR, revealing a mixture of unsaturated (80.5%) and saturated (18.7%) fatty acids. Linoleic (45.3%) and oleic (33.5%) acid were the major unsaturated fatty acids identified, while palmitic acid (14.3%) was the major saturated fatty acid. The larvicidal effects of A. salzmannii seed oil were evaluated against third-instar larvae of Aedes aegypti (Linn.). The oil exhibited moderate larvicidal activity, with a LC50 of 569.77 ppm (95% CI = 408.11 to 825.88 ppm). However, when the cytotoxic effects of the oil were evaluated, no expressive antiproliferative effects were observed in tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia), HL-60 (human promyelocytic leukemia), and non-tumor cell line PBMC (peripheral blood mononuclear cells), with IC50 values > 50 µg·mL-1. This is the first study to evaluate the chemical composition, larvicidal and cytotoxic activity of A. salzmannii seed oil

Estudo das propriedades anticâncer da piplartina / Studying the anticancer properties of piplartine

A piplartina é um alcalóide/amida conhecido encontrado em espécies do gênero Piper com propriedade citotóxica interessante. Para avaliar o seu potencial antineoplásico, um estudo farmacológico de suas propriedades anticâncer foi realizado em vários modelos biológicos. A piplartina apresentou potente atividade citotóxica em todas as linhagens tumorais testadas. Por comparação da citotoxicidade de moléculas com estruturas relacionadas com a piplartina, foi identificado que a presença da carbolina α,β-insaturada do anel amídico é essencial para a sua atividade citotóxica. Em células mononucleares de sangue periférico de doadores saudáveis expostas a piplartina induziu apoptose em células leucêmicas HL-60, com participação da via intrínseca, de maneira dependente da concentração, como observado pelo padrão de morfologia celular, integridade da membrana citoplasmática, alteração no potencial transmembrânico da mitocôndria e aumento da fragmentação do DNA. Na análise do ciclo celular, foi observado bloqueio na fase G2. A piplartina foi capaz de induzir dano ao DNA em células V79, como observado pelo ensaio do cometa alcalino e neutro. Seu mecanismo de ação genotóxico parece ser semelhante ao da sua atividade citotóxica. Não foi observada atividade mutagênica, com ou sem ativação metabólica (S9), nas linhagens de Salmonella (modelo procariótico) testadas. Por outro lado, a piplartina foi mutagênica e recombinogênica em linhagens de Saccharomyces cerevisiae (modelo eucariótico)...