3.4.2. FDA-approved drugs library docking
hypertension
HYPERTENSION
The highest LibDock score for PPARα was 119.43 shown by Forasartan. The key residues for binding interaction between Forasartan and PPARα were Met24, Cys80, Thr87, Ile121, Leu125, and Val128. Thr87 formed a carbon-hydrogen bond whereas Ile12, Met24, Cys80, Leu125, and Val128 were forming hydrophobic interactions with Forasartan. It is used as an antihypertensive agent to treat hypertension and also is a selective angiotensin II antagonist, type 1; because angiotensin induces vasoconstriction, inhibiting this receptor reduces vasoconstriction, which consequently also decreases vascular resistance [The highest docked FDA-approved drug for PPAR was Raltitrexed, which had a LibDock score of 151.057. The binding interaction of Raltitrexed with residues: Leu49, Gly52, Phe58, His60, Arg82, Ile135, and Glu137 of PPARγ were noted. The residues of PPARγ: Gly52, Arg74, and Glu137 were developing carbon-hydrogen bonds and conventional hydrogen bonds whereas the other residues Gly52, Phe58, His60, Arg82, and Glu137 were forming hydrophobic interactions with Raltitrexed. Leu49 and Ile75 were involved in both types of interaction. It is a thymidylate synthase (TS) inhibitor that inhibits L1210 cell growth that belongs to the antimetabolite class of cytotoxic medicines (IC50 = nM) [The 2D interaction diagrams of (A) APHM13 with PPARα, (B) Forasartan with PPARα, (C) Lanifibranor with PPARα, (D) Raltitrexed with PPARγ, (E) Lanifibranor with PPARγ, (F) Iloprost with PPARδ, (G) Lifitegrast with PPARδ and (H) Lanifibranor with PPARδ sketched through Discovery Studio.The top docked FDA-approved drug for PPARδ was Lifitegrast. It showed the LibDock score of 162.505. Two hydrogen bonds were established during docking of Lifitegrast with PPARδ. The PPARδ residues Trp228, Cys249, Thr252, Glu255, Ala306, and Tyr437 formed hydrogen bonds. All other residues such as Trp228, Arg248, Leu249, Cys251, His287, Leu303, Val305, Val312, Ile327, Ile328, and His413 were involved in hydrophobic contacts. Lifitegrast is an antagonist that inhibits the T cell-mediated inflammatory cycle by acting as a direct competitive antagonist of ICAM-1 to LFA-1 binding [