Synthesis and Initial Testing of Novel Antimalarial and Antitubercular Isonicotinohydrazides
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Date
2022
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier B.V.
Abstract
Malaria and tuberculosis (TB) though curable and preventable, remain serious public health problems globally,
with devastating consequences. Co-infection of these two deadly diseases worsens the situation and particularly
makes treatment very difficult. The current mainstay for malaria treatment is gradually losing their potency due
to the development of resistance. Macobacterium tuberculosis (MTB) has developed Multi-drug Resistance (MDR)
and Extensive Drug Resistance (XDR) to current antitubercular drugs due to patient incompliance resulting from
long treatment regimen. A small library of isonicotinohydrazide were synthesised by incorporating 1,2,4,5-
tetraoxane and hydrazine moieties. Evaluation of the compounds gave antimalarial activities in the range 0.060
± 0.033–0.491 ± 0.012 μM against 3D7 strain of Plasmodium falciparum. We assessed antimycobacterial activity
of selected compounds against the standard Mycobacterium tuberculosis reference strain H37Rv and M. aurum (a
non-tuberculous mycobacteria) using the microplate Alamar blue (MABA) assay and found four compounds to be
very potent against H37Rv but largely inactive against Macobacterium aurum. We followed up to estimate the
minimum inhibitory concentrations of these active compounds and tested them against clinical M. tuberculosis
strains resistant to isoniazid (INH) and rifampicin (RIF). The MICs of the active compounds against H37Rv were
between 0.003 and 0.5 mg/mL however, they were largely inactive against drug resistant clinical strains except
for the INH mono-resistant resistant strain which was very active with compounds 5 and 8 possessing MICs of
0.125 mg/mL.
Description
Research Article
Keywords
Isonitinohydrazides, Tetraoxanes, Molecular hybridization