Antimicrobial resistance (AMR) is a threat to the prevention and treatment of the increasing range of infectious diseases. There is therefore the need for renewed efforts into antimicrobial discovery and development to combat the menace. The antimicrobial activity of plumbagin isolated from roots of Plumbago zeylanica against selected organisms was evaluated for resistance modulation antimicrobial assay, time-kill kinetics assay, and inhibition of biofilm formation. The minimum inhibitory concentrations (MICs) of plumbagin and standard drugs were determined via the broth microdilution method to be 0.5 to 8 μg/mL and 0.25–128 μg/mL, respectively. In the resistance modulation study, MICs of the standard drugs were redetermined in the presence of subinhibitory concentration of plumbagin (4 μg/mL), and plumbagin was found to either potentiate or reduce the activities of these standard drugs with the highest potentiation recorded up to 12-folds for ketoconazole against Candida albicans. Plumbagin was found to be bacteriostatic and fungistatic from the time-kill kinetics study. Plumbagin demonstrated strong inhibition of biofilm formation activity at concentrations of 128, 64, and 32 μg/mL against the test microorganisms compared with ciprofloxacin. Plumbagin has been proved through this study to be a suitable lead compound in antimicrobial resistance drug development.

No abstract

Introduction. In the management of hypertension (a cardiovascular disease and the leading metabolic risk factor in noncommunicable diseases) with herbal medicines, efficacy and safety are of uttermost concern. This study sought to establish hypotensive, antihypertensive, drug interaction, and safety for use of the aqueous leaf extracts of Annona muricata (AME), Persea americana (PAE), or their combination products (CAPE). Methodology. Systolic and diastolic blood pressure (SBP and DBP), mean arterial blood pressure (MAP), and heart rate (HR) were measured in normotensive Sprague-Dawley rats treated with 50–150 mg/kg of AME, PAE, or CAPE to establish a hypotensive effect. “Combination index” was calculated to establish interaction between AME and PAE. The antihypertensive effect of CAPE was established by measuring SBP, DBP, MAP, and HR in ethanol-sucrose- and epinephrine-induced hypertension. Full blood count, liver and kidney function tests, and urinalysis were determined in ethanol/sucrose-induced hypertension to establish safety for use. Results. AME, PAE, and CAPE significantly ( p ≤ 0.001 ) decreased BP in both normotensive and hypertensive animals. Effects of CAPE 1, CAPE 2, and CAPE 3 were synergistic (combination indices of 0.65 ± 0.07, 0.76 ± 0.09, and 0.87 ± 0.07, respectively). There was a significant decrease ( p ≤ 0.01 − 0.001 ) in SBP and MAP with 100 mg/kg CAPE 1 and 75 mg/kg CAPE 2 treatment in hypertension as well as with nifedipine ( p ≤ 0.001 ) treatment. Epinephrine-induced hypertension in anesthetized cats was significantly and dose-dependently inhibited ( p < 0.05 − 0.001 ) by 25–100 mg/ml CAPE 1 and 37.5–75 mg/ml CAPE 2. CAPE administration had no deleterious effect ( p > 0.05 ) on full blood count, liver and kidney function, and urine composition in hypertensive rats. Conclusion. The aqueous leaf extracts of Annona muricata, Persea americana, and their combination products possess antihypertensive properties, with combination products showing synergism and safety with use.

CYP17A1 is an enzyme that plays a major role in steroidogenesis and is critically involved in the biosynthesis of steroid hormones. Therefore, it remains an attractive target in several serious hormone-dependent cancer diseases, such as prostate cancer and breast cancer. The medicinal chemistry community has been committed to the discovery and development of CYP17A1 inhibitors for many years, particularly for the treatment of castration-resistant prostate cancer. The current Perspective reflects upon the discovery and evaluation of non-steroidal CYP17A1 inhibitors from a medicinal chemistry angle. Emphasis is placed on the structural aspects of the target, key learnings from the presented chemotypes, and design guidelines for future inhibitors.