Hydroxylated metabolites of the antimalarial drug primaquine. Oxidation and redox cycling.

ABSTRACT The identification of 1β-hydroxynorgestrel among the urinary metabolites of dl-norgestrel and the facile transformation of this compound under mild alkaline conditions to a potentially oestrogenic phenol provide an experimental basis for the conclusion advanced by others that the oestrogens present in the urine of subjects treated with synthetic progestens are artifacts formed during analytical work-up. A method has been devised which eliminates 1-hydroxylated metabolites as potential sources of phenolic artifacts. This method is based on the reduction by NaBH4 of the 1-hydroxy-4-en-3-one grouping in the A ring thereby excluding the possibility of aromatization during later fractionation on a basic ion exchange resin that separates neutral from phenolic metabolites. In the urines of women treated with 14C-dl-nogestrel, only 0.17–0.27% of the dose is found to have phenolic properties when this method is used. Two of the phenolic metabolites, 18-homoethynyloestradiol and 16β-hydroxy-18-homoethynyloestradiol, are present in amounts smaller than 0.01 % of the dose. Without the reduction steps the percentages are noticeably higher, indicating artifact formation under alkaline conditions. Similar results were obtained with urines from African Green Monkeys (Cercopithecus Aethiops) that had been dosed with 14C-dl-norgestrel. Radiolabelled 18-homoethynyloestradiol and 16β-hydroxy-18-homoethynyloestradiol were isolated from monkey urine and their identity confirmed by gas chromatography-mass spectrometry.

Download Full-text

Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

10.31222/osf.io/78mbt ◽

2020 ◽

Author(s):

Sanaa Bardaweel

Keyword(s):

Clinical Trials ◽

Drug Discovery ◽

Antimalarial Drug ◽

Drug Repurposing ◽

Spike Protein ◽

Diabetic Patients ◽

Potential Drug ◽

Chemokine Production ◽

Drug Discovery And Development ◽

Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

Download Full-text