Discovery of Novel Myristic Acid Derivatives as N-Myristoyltransferase Inhibitors: Design, Synthesis, Analysis, Computational Studies and Antifungal Activity.

In recent years, N-Myristoyltransferase (NMT) has been identified as a new target for the treatment of fungal infections. It is observed that at present, there are increased rates of morbidity and mortality due to fungal infections. Hence, a series of novel myristic acid derivatives were designed via molecular docking studies and ADMET studies by targeting NMT (N-Myristoyltransferase). The designed myristic acid derivatives were synthesized by converting myristic acid into myristoyl chloride and coupling it with aryl amines to yield corresponding myristic acid derivatives. The compounds were purified and characterized via FTIR, NMR and HRMS spectral analyses. In this study, we carried out a target NMT inhibition assay. In the NMT screening assay results, the compounds 3u, 3m and 3t showed better inhibition compared to the other myristic acid derivatives. In an in vitro antifungal evaluation, the myristic acid derivatives were assessed against Candida albicans and Aspergillus niger strains by determining their minimal inhibitory concentrations (MIC50). The compounds 3u, 3k, 3r and 3t displayed superior antifungal capabilities against Candida albicans, and the compounds 3u, 3m and 3r displayed superior antifungal capabilities against Aspergillus niger compared to the standard drug FLZ (fluconazole). Altogether, we identified a new series of antifungal agents.

Novel Indole-Tethered Chromene Derivatives: Synthesis, Cytotoxic Properties, and Key Computational Insights.

Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N-alkyl-1H-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60-65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC50 values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

Prescribing pattern of antihypertensive drugs in diabetic patients of Southern Province, Kingdom of Saudi Arabia / El patrón de prescripción de los fármacos antihipertensivos en los pacientes diabéticos de la Provincia del Sur, Reino de Arabia Saudita

Background. Hypertension is extremely prevalent in patients with diabetes. Limited data exist on utilization patterns of antihypertensive in this population are consistent with evidence-based practice guidelines. Objective. To evaluate utilization patterns of antihypertensive agents among diabetic patients with hypertension. Design. retrospective descriptive cross sectional. Patients / Participants. 149 patients with diabetes and hypertension from outpatient department at Family Medicine Hospital, Ahaderfieda. Khamis Mushait, K.S.A. Results. Over 43% of patients were receiving calcium channel blockers (CCB), 36.2 % of received angiotensin converting enzyme inhibitors (ACEI), followed by angiotensin receptor blockers (ARBs) (34.9%), diuretics (34.2%) and Beta-blockers (16.2%). Patients on monotherapy were mostly receiving CCB (34.3%) and ACEI (29.9%). The majority (55.03%) of treated patients were on multidrug regimens. In patients with coronary artery disease (CAD), a diuretic with ACEI (25%) and calcium hannel blocker with angiotensin receptor blocker (25%) was most commonly prescribed. Conclusions. Patterns of antihypertensive therapy were generally consistent with international guidelines. Areas of improvement include increasing ACEI/ARB and diuretic use, decreasing the number of untreated patients, and increasing the proportion of patients with controlled BP in this population

Antecedentes. La hipertensión es muy frecuente en los pacientes con diabetes. Existen datos limitados sobre los patrones de utilización de antihipertensivos en esta población consistentes con las guías de práctica basadas en la evidencia. Objetivo. Evaluar los patrones de utilización de antihipertensivos en los pacientes diabéticos con hipertensión Diseño. Estudio retrospectivo descriptivo transversal. Pacientes / Participantes. 149 pacientes con diabetes e hipertensión, del departamento de pacientes ambulatorios en el Hospital de Medicina Familiar, Ahaderfieda. Khamis Mushait, K.S.A. Resultados. Más del 43% de los pacientes estaban recibiendo bloqueadores del canal de calcio (CCB), el 36,2% recibían inhibidores de la enzima convertidora de angiotensina (IECA), seguido de los bloqueadores de los receptores de angiotensina (BRA) (34,9%), diuréticos (34,2%) y bloqueadores β (16,2 %). Los pacientes en monoterapia fueron la mayoría recibiendo CCB (34,3%) e IECA (29,9%). La mayoría (55,03%) de los pacientes tratados se encontraban en regímenes de múltiples fármacos. En los pacientes con enfermedad de la arteria coronaria (CAD), se les prescribió con mayor frecuencia diurético con IECA (25%) y bloqueador de canales de calcio con bloqueador del receptor de angiotensina (25%). Conclusiones. Los patrones de utilización de antihipertensivos fueron generalmente consistentes con las directrices internacionales. Las áreas de mejora incluyen el aumento de IECA / ARB y el uso de diuréticos, disminuyendo el número de pacientes no tratados, y el aumento de la proporción de pacientes con PA controlada en esta población