Synthesis and biological evaluation of cyanoguanidine derivatives of loratadine

Bioorg Med Chem Lett. 2012 Oct 1;22(19):6076-80. doi: 10.1016/j.bmcl.2012.08.041. Epub 2012 Aug 16.

Abstract

Cyanoguanidine derivatives of loratadine (3a-i) were synthesized and screened for antitumor and anti-inflammatory activity. The most promising compound 3c (R=n-C(8)H(17)) possessed at least twofold higher in vitro cytotoxicity than 5-fluorouracil against mammary (MCF-7 and MDA-MB 231) as well as colon (HT-29) carcinoma cells. The mode of action, however, is so far unclear. The participation of the COX-1/2 enzymes on the cytotoxicity, however, is very unlikely. Nevertheless all compounds showed stronger in vivo anti-inflammatory activity than ibuprofen in the xylene-induced ear swelling assay in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Ear Diseases / chemically induced
  • Ear Diseases / drug therapy*
  • Guanidines / chemistry*
  • HT29 Cells
  • Humans
  • Loratadine / analogs & derivatives*
  • Loratadine / chemistry
  • Loratadine / pharmacology*
  • MCF-7 Cells
  • Male
  • Mice
  • Mice, Inbred Strains
  • Molecular Structure
  • Structure-Activity Relationship
  • Xylenes

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Guanidines
  • Xylenes
  • Loratadine
  • dicyandiamido