Discovering the natural source-derived antihypertensive compounds aspiring current therapeutic targets by computer-based drug design.

Hypertension, a primary global health concern, heightens the risk of heart, brain, and kidney diseases and contributes to premature mortality. The present paper thoroughly explores the potential therapeutic use of natural compounds, drawing on Avicenna's ancient medical philosophy to highlight the role of bodily humor imbalances and lifestyle factors in hypertension. A key aspect of our study is using a computer-aided drug design (CADD) approach, which we employ to identify novel antihypertensive bio-compounds, focusing on current therapeutic targets, including angiotensin I-converting enzyme, angiotensin II receptor, and calcium channel. Comprehensive molecular docking and dynamic simulations were employed to evaluate the binding interactions and affinities of these compounds with key hypertension-related proteins. Using Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) for binding free energy calculations and ADMET analysis to enhance the precision of our findings, we identified standout candidates from the AVICENNA database, including FDB014401, FDB014715, and FDB014560. These compounds exhibited outstanding docking scores, ranging from -9.60 to -11.60 kcal/mol across three targets, highlighting their potential to act as potent inhibitors of the intended proteins. Molecular dynamics simulations reveal that these bio-compounds maintain stable interactions with target proteins over 100 ns, with no significant conformational alterations, underscoring their promise as viable antihypertensive agents. Due to our study's thoroughness, these findings provide a solid foundation for forthcoming pre-clinic and empiric studies, and the successful use of CADD in our research instills confidence in its potential to discover novel, naturally derived antihypertensive therapies.