Synthesis and structure guided evaluation of estrogen agonist and antagonist activities of some new tetrazolyl indole derivatives.
Several regioisomeric tetrazolyl indole derivatives with structurally modified alkyl substituents at the tetracyclic indole nitrogen containing N-ethyl amino tetrazole moiety have been synthesized and screened for their ER binding affinity, agonist (estrogenic), antagonist (antiestrogenic) and anti-implantation activities. N-2 regioisomers were found to be moderately antagonists and one compound showed 100% contraceptive efficacy at 10 mg/kg dose. Molecular docking studies carried out in comparison to estradiol and raloxifene showed different binding modes of the two regioisomers to the binding site.
D000818:Animals; D003281:Contraceptives, Postcoital / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D004965:Estrogen Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004967:Estrogens / Q000819:agonists*; D005260:Female; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D051381:Rats; D011960:Receptors, Estrogen / Q000737:chemistry / Q000378:metabolism; D013777:Tetrazoles / Q000737:chemistry*
D003281:Contraceptives, Postcoital; D004965:Estrogen Antagonists; D004967:Estrogens; D007211:Indoles; D008024:Ligands; D011960:Receptors, Estrogen; D013777:Tetrazoles