Macrofilaricidal Benzimidazole-Benzoxaborole Hybrids As an Approach to the Treatment of River Blindness: Part 1. Amide Linked Analogs

Overview

Journal ACS Infect Dis

Specialties Infectious Diseases
Microbiology
Pharmacology

Date 2019 Dec 27

PMID 31876154

Citations 5

Authors

Tsutomu Akama

Yvonne R Freund

Pamela W Berry

David S Carter

Eric E Easom

Kurt Jarnagin

Christopher S Lunde

Jacob J Plattner

Fernando Rock

Rianna Stefanakis

Chelsea Fischer

Christina A Bulman

Kee Chong Lim

Brian M Suzuki

Nancy Tricoche

Abdelmoneim Mansour

Utami DiCosty

Scott McCall

Ben Carson

John W McCall

James McKerrow

Marc P Hubner

Sabine Specht

Achim Hoerauf

Sara Lustigman

Judy A Sakanari

Robert T Jacobs

Affiliations

Soon will be listed here.

Abstract

A series of benzimidazole-benzoxaborole hybrid molecules linked via an amide linker are described that exhibit good activity against , a filarial nematode responsible for the disease onchocerciasis, also known as river blindness. The lead identified in this series, (AN8799), was found to have acceptable pharmacokinetic properties to enable evaluation in animal models of human filariasis. Compound was effective in killing , , and worms present in Mongolian gerbils when dosed subcutaneously as a suspension at 100 mg/kg/day for 14 days but not when dosed orally at 100 mg/kg/day for 28 days. The measurement of plasma levels of at the end of the dosing period and at the time of sacrifice revealed an interesting dependence of activity on the extended exposure for both and the positive control, flubendazole.

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