Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates

Roman N Naumov; Siva S Panda; Adel S Girgis; Riham F George; Michel Farhat; Alan R Katritzky

doi:10.1016/j.bmcl.2015.04.023

Synthesis and QSAR study of novel anti-inflammatory active mesalazine-metronidazole conjugates

Bioorg Med Chem Lett. 2015 Jun 1;25(11):2314-20. doi: 10.1016/j.bmcl.2015.04.023. Epub 2015 Apr 13.

Authors

Roman N Naumov¹, Siva S Panda², Adel S Girgis³, Riham F George⁴, Michel Farhat¹, Alan R Katritzky⁵

Affiliations

¹ Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, United States.
² Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, United States. Electronic address: sspanda12@gmail.com.
³ Pesticide Chemistry Department, National Research Centre, Dokki, Giza 12622, Egypt.
⁴ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
⁵ Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, United States; Chemistry Department, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

PMID: 25937011
DOI: 10.1016/j.bmcl.2015.04.023

Abstract

Novel, mesalazine, metronidazole conjugates 6a-e with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates exhibit comparable anti-inflammatory activity with parent drugs and (b) the potent bis-conjugates show no visible stomach lesions. 3D-pharmacophore and 2D-QSAR modeling support the observed bio-properties.

Keywords: Amino acids; Anti-inflammatory; Conjugates; Mesalazine; Metronidazole; QSAR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / adverse effects
Anti-Inflammatory Agents / chemistry
Anti-Inflammatory Agents / pharmacology*
Indomethacin / toxicity
Mesalamine / adverse effects
Mesalamine / chemistry
Mesalamine / pharmacology*
Metronidazole / adverse effects
Metronidazole / chemistry
Metronidazole / pharmacology*
Mice
Molecular Structure
Quantitative Structure-Activity Relationship
Stomach Ulcer / chemically induced

Substances

Anti-Inflammatory Agents
Metronidazole
Mesalamine
Indomethacin