title: Synthesis and structure guided evaluation of estrogen agonist and antagonist activities of some new tetrazolyl indole derivatives.
abstract: 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.
authors.affiliation: Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India.
authors.forename: Uma Sharan
authors.initials: US
authors.lastname: Singh
authors.forename: Ravi
authors.initials: R
authors.lastname: Shankar
authors.forename: Gaya P
authors.initials: GP
authors.lastname: Yadav
authors.forename: Geetika
authors.initials: G
authors.lastname: Kharkwal
authors.forename: Anila
authors.initials: A
authors.lastname: Dwivedi
authors.forename: Govind
authors.initials: G
authors.lastname: Keshri
authors.forename: M M
authors.initials: MM
authors.lastname: Singh
authors.forename: P R
authors.initials: PR
authors.lastname: Moulik
authors.forename: K
authors.initials: K
authors.lastname: Hajela
mesh_terms: 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*
chemical_list: D003281:Contraceptives, Postcoital; D004965:Estrogen Antagonists; D004967:Estrogens; D007211:Indoles; D008024:Ligands; D011960:Receptors, Estrogen; D013777:Tetrazoles