title: Design and synthesis of 3-(3-((9H-carbazol-4-yl)oxy)-2-hydroxypropyl)-2-phenylquinazolin-4(3H)-one derivatives to induce ACE inhibitory activity.
abstract: In an attempt to develop a new class of cardiovascular drugs, a series of novel carbazolyloxy phenylquinazoline derivatives 9a-g have been synthesized and evaluated as angiotensin converting enzyme (ACE) inhibitors. Most of these compounds exhibited activity as significant ACE inhibitors and three compounds (9b, 9c & 9e) showed maximum inhibitory potency in enzyme based assays. To render support to the experimental results, a series of quinazolinone derivatives were docked into active site of ACE and identified the probable binding modes compared to Lisinopril. Also we have identified common pharmacophore hypothesis (AAADDRR) among the best docked conformers of most potent compounds in a series of compounds. The most potent 9b, 9c, 9e compounds shared common active site with the Lisinopril binding site and retained the key active site residue interactions. The obtained results from pharmacological and molecular modeling studies can be utilized for further optimization of identified hits for selective inhibition of ACE.
authors: Organic Chemistry Division II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors: Ramineni
authors: R
authors: Venkatesh
authors: Organic Chemistry Division II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors: Suresh
authors: S
authors: Kasaboina
authors: Organic Chemistry Division II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors: Hanmant K
authors: HK
authors: Gaikwad
authors: Centre for Molecular Modeling, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors: Sridhara
authors: S
authors: Janardhan
authors: Organic Chemistry Division II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors: Rajashaker
authors: R
authors: Bantu
authors: Organic Chemistry Division II (CPC), CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India. Electronic address: lnagarapuiict@yahoo.com.
authors: Lingaiah
authors: L
authors: Nagarapu
authors: Centre for Molecular Modeling, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
authors: G Narahari
authors: GN
authors: Sastry
authors: Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors: Sanjay K
authors: SK
authors: Banerjee
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002227:Carbazoles; D052999:Quinazolinones; D007703:Peptidyl-Dipeptidase A
keywords: ACE inhibitory activity; Docking studies; Lisinopril; Quinazolinone derivatives