Synthesis of some heterofunctionalized penicillanic acid derivatives and investigation of their biological activities

Arch Pharm (Weinheim). 2014 Mar;347(3):200-20. doi: 10.1002/ardp.201300280. Epub 2013 Dec 2.

Abstract

6-Substituted amino-penicillanic acid esters were synthesized starting with 6-apa. The compounds containing a 1,3-thiazole- or 1,3-thiazolidinone nucleus linked to the penicillanic acid skeleton via a hydrazino linkage were obtained from 6-apa. The treatment of carbonylamino and carbonothioylamino compounds with 4-chlorophenacyl bromide or ethyl bromoacetate gave 6-bis{4-[1,3-thiazol(idinone)amino]benzoyl}amino derivatives of 6-apa. Benzyl derivatives were synthesized in several steps, starting with 4-aminobenzoyl chloride. The treatment of 4-{[3-benzyl-4-oxo-1,3-thia(oxa)zolidin-2-ylidene]amino}benzoyl chlorides with 6-apa in ethanolic solution produced the 6-[bis(4-{[3-benzyl-4-oxo-1,3-thiazolidin-2-ylidene]amino}benzoyl)amino] derivative of penicillanic acid, while the reaction of the same intermediates in DMF gave the mono-substituted amino derivative of 6-apa. The synthesized compounds were screened for their biological activities, and some of them were found to possess good to moderate antimicrobial activity. Moreover, some of the compounds displayed antiurease, anti-β-lactamase, and/or antilipase activities.

Keywords: 1,3-Oxa(thia)zole; 6-Amino penicillanic acid; Anti β-lactamase activity; Anti-urease activity; Antilipase activity; Antimicrobial activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Lipase / antagonists & inhibitors
  • Lipase / metabolism
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / chemical synthesis*
  • Penicillanic Acid / pharmacology*
  • Structure-Activity Relationship
  • Urease / antagonists & inhibitors
  • Urease / metabolism
  • beta-Lactamase Inhibitors / chemical synthesis
  • beta-Lactamase Inhibitors / pharmacology

Substances

  • Anti-Infective Agents
  • Enzyme Inhibitors
  • beta-Lactamase Inhibitors
  • Penicillanic Acid
  • Lipase
  • Urease