Delapril Hydrochloride

Backround: The effect of antihypertensive drugs on glucose homeostasis and insulin resistance remains an issue under investigation. There is evidence that renin-angiotensin system (RAS) blockers may favorably affect glucose metabolism, while treatment with calcium channel blockers (CCBs) is considered to have an overall neutral metabolic effect. However, the effects on glycemic indices may differ among agents within the same class of antihypertensive drugs. Objective: To evaluate the effects of different fixed-dose single pill combinations of RAS blockers with CCBs on homeostatic model assessment for insulin resistance (HOMA-IR). Methods: Drug-naive patients with arterial hypertension (AH) and impaired fasting glucose (IFG) were randomly allocated to open-label fixed, single pill combinations of valsartan 160 mg/day plus amlodipine 5 mg/day (VAL/AMLO group, n = 54), delapril 30 mg/day and manidipine 10 mg/day (DEL/MANI group, n = 53) or telmisartan 80 mg/day and amlodipine 5 mg/day (TEL/AMLO group, n = 51) for 12 weeks. Glycemic indices and HOMA-IR were determined at baseline and post-treatment. Results: A total of 158 patients were included. All treatment combinations effectively reduced blood pressure (systolic and diastolic) to similar levels (all p < 0.001). A decrease in the HOMA-IR index by 22.55% (p < 0.01) was noted following treatment with TEL/AMLO, while an increase by 1.4% (p = 0.57) and 12.65% (p = 0.072) was observed in the VAL/AMLO group and the DEL/MANI group, respectively. These changes were significantly different between TEL/AMLO and DEL/MANI (p < 0.05) as well as between TEL/AMLO and VAL/AMLO (p < 0.001). Conclusions: Despite similar antihypertensive action, the effect of fixed, single pill combinations with TEL/AMLO, VAL/AMLO and DEL/MANI on insulin resistance is in favor of TEL/AMLO. Trial registration: The study protocol was published online in https://diavgeia.gov.gr/ (No: ΒΘ6Σ46906Η-ΑΕΣ) via the Ministry of Digital Governance, after receiving approval from the Scientific Council and Administrative Council of University Hospital of Ioannina (No. of approval: 1/12-06-2014 (issue 150). https://diavgeia.gov.gr/decision/view/%CE%92%CE%986%CE%A346906%CE%97- %CE%91%CE%95%CE%A3 https://diavgeia.gov.gr/doc/%CE%92%CE%986%CE%A346906%CE%97- %CE%91%CE%95%CE%A3?inline=true

The recent new contagion coronavirus 2019 (COVID-19) disease is a new generation of severe acute respiratory syndrome coronavirus-2 SARS-CoV-2 which infected millions confirmed cases and hundreds of thousands death cases around the world so far. Molecular docking combined with molecular dynamics is one of the most important tools of drug discovery and drug design, which it used to examine the type of binding between the ligand and its protein enzyme. Global reactivity has important properties, which enable chemists to understand the chemical reactivity and kinetic stability of compounds. In this study, molecular docking and reactivity were applied for eighteen drugs, which are similar in structure to chloroquine and hydroxychloroquine, the potential inhibitors to angiotensin-converting enzyme (ACE2). Those drugs were selected from DrugBank. The reactivity, molecular docking and molecular dynamics were performed for two receptors ACE2 and [SARS-CoV-2/ACE2] complex receptor in two active sites to find a ligand, which may inhibit COVID-19. The results obtained from this study showed that Ramipril, Delapril and Lisinopril could bind with ACE2 receptor and [SARS-CoV-2/ACE2] complex better than chloroquine and hydroxychloroquine. This new understanding should help to improve predictions of the impact of such alternatives on COVID-19.Communicated by Ramaswamy H. Sarma.