Design, synthesis and evaluation of novel 2-hydroxypyrrolobenzodiazepine-5, 11-dione analogues as potent angiotensin converting enzyme (ACE) inhibitors

Dinesh Addla, Anvesh Jallapally, Abhinav Kanwal, Balasubramanian Sridhar, Sanjay K. Banerjee, Srinivas Kantevari

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

A series of novel 10-substituted 2-hydroxypyrrolobenzodiazepine-5,11-diones designed through structure based rational hybridization approach, synthesized by the cyclodehydration of isotonic anhydride with (2S,4R)-4-hydroxypyrrolidine- 2-carboxylic acid followed by N-substitution, were evaluated as angiotensin converting enzyme (ACE) inhibitors. Among all the new compounds screened (2R,11aS)-10-((4-bromothiophen-2-yl)methyl)-2-hydroxy-2,3-dihydro-1H-benzo[e] pyrrolo[1,2-a][1,4]diazepine-5,11(10H,11aH)dione, 5v (IC50: 0.272 μM) emerged as most active non-carboxylic acid ACE inhibitor with minimal toxicity comparable to clinical drugs Lisinopril, Benazepril and Ramipril. Favorable binding characteristics in docking studies also supported the experimental results.

Original languageEnglish
Pages (from-to)4485-4493
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume21
Issue number15
DOIs
Publication statusPublished - 01-08-2013

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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