Synthesis and antifilarial activity of chalcone-thiazole derivatives against a human lymphatic filarial parasite, Brugia malayi

Koneni V Sashidhara; K Bhaskara Rao; Vikas Kushwaha; Ram K Modukuri; Richa Verma; P K Murthy

doi:10.1016/j.ejmech.2014.05.029

Synthesis and antifilarial activity of chalcone-thiazole derivatives against a human lymphatic filarial parasite, Brugia malayi

Eur J Med Chem. 2014 Jun 23:81:473-80. doi: 10.1016/j.ejmech.2014.05.029. Epub 2014 May 12.

Authors

Koneni V Sashidhara¹, K Bhaskara Rao², Vikas Kushwaha³, Ram K Modukuri², Richa Verma³, P K Murthy⁴

Affiliations

¹ Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh 226031, India. Electronic address: [email protected].
² Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, Uttar Pradesh 226031, India.
³ Division of Parasitology, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
⁴ Division of Parasitology, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: [email protected].

PMID: 24863844
DOI: 10.1016/j.ejmech.2014.05.029

Abstract

Here we report the synthesis of novel chalcone-thiazole compounds and their antifilarial activity. The antifilarial properties of these hybrids were assessed against microfilariae as well as adult worms of Brugia malayi. Among all the synthesized compounds, only two compounds, namely 4g and 4n were identified to be promising in vitro. These active compounds were tested in B. malayi-jird (Meriones unguiculatus) and B. malayi-Mastomys coucha models. Compound 4n showed 100% embryostatic effect and 49% macrofilaricidal in jirds and M. coucha models, respectively. This study provides a new structural clue for the development of novel antifilarial lead molecules.

Keywords: Albendazole; Brugia malayi; Diethylcarbamazine; Ivermectin; Macrofilariae; Microfilariae.

Publication types

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

MeSH terms

Animals
Brugia malayi / drug effects*
Chalcone / analogs & derivatives*
Chalcone / chemistry
Chalcone / pharmacology*
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Filariasis / drug therapy*
Filariasis / parasitology
Filaricides / chemical synthesis*
Filaricides / chemistry
Filaricides / pharmacology*
Gerbillinae
Male
Molecular Structure
Murinae
Parasitic Sensitivity Tests
Structure-Activity Relationship
Thiazoles / chemistry
Thiazoles / pharmacology*

Substances

Filaricides
Thiazoles
Chalcone