Molecular docking analysis of AGTR1 antagonists

Area of Science:

• Pharmacology
• Medicinal Chemistry
• Cardiovascular Research

Background:

• Cardiovascular diseases (CVDs) are a major global health concern, leading to significant mortality and morbidity.
• The renin-angiotensin system plays a critical role in regulating cardiovascular and renal functions.
• Current synthetic treatments for CVDs, like ACE inhibitors and ARBs, can cause adverse effects, necessitating alternative therapeutic strategies.

Purpose of the Study:

• To identify novel natural compounds that can inhibit the type-1 angiotensin II receptor (AGTR1).
• To explore natural compounds as potential therapeutic agents for managing cardiovascular diseases (CVDs).

Main Methods:

• In silico screening of natural compounds from the ZINC database against the AGTR1 active site.
• Comparative analysis of binding energies between identified natural compounds and standard AGTR1 inhibitors.
• Evaluation of drug-like characteristics of the identified hit compounds.

Main Results:

• Five natural compounds (ZINC85625504, ZINC62001623, ZINC70666587, ZINC06624086, and ZINC95486187) exhibited binding energies comparable to established AGTR1 inhibitors.
• These compounds demonstrated interactions with key residues within the AGTR1 active site.
• The identified compounds possess favorable drug-like properties.

Conclusions:

• The identified natural compounds show significant potential as AGTR1 inhibitors.
• These compounds represent promising candidates for the development of new therapeutic strategies for cardiovascular diseases (CVDs).
• Further preclinical and clinical investigations are warranted to validate their efficacy and safety.