6-Methyl-4,5-dihydropyridazin-3(2H)-one Derivatives as Antimycobacterial Agents

3. International Health Sciences and Innovation, Ankara, Türkiye, 12 - 13 Ocak 2021, cilt.0, sa.0, ss.122-123

Mycobacterium tuberculosis (Mtb) is the organism that causes Tuberculosis (TB), which is

among the diseases with the highest mortality rate worldwide. Globally, 2.0 million new and

relapse TB cases were identified by a WHO-recommended rapid diagnostic test in 2019.

Therefore, developing new active agents to combat TB is an urgent need.

4,5-Dihydropyridazin-3(2H)-one derivatives have been extensively investigated for their

potential as anti-TB drug candidates. In the light of this consideration and our previous study,

we designed and synthesized some new 6-methyl-4,5-dihydropyridazin-3(2H)-ones,

investigated their antimycobacterial activities.

4-Thiazolidinone and 1,3,4-oxadiazole derivatives were obtained by the cyclization of 2,4-

dichlorophenyl substituted hydrazone derivative with thioacetic acid and acetic anhydride,

respectively (Figure). In vitro antimycobacterial activity assays of the synthesized

compounds were carried out using the by agar dilution method against M. tuberculosis H37Rv.

N'-(substitutedbenzylidene)-2-(3-methyl-6-oxo-5,6-dihydropyridazin-1(4H)-

yl)acetohydrazide derivatives, N-(2-(2,4-dichlorophenyl)-4-oxothiazolidin-3-yl)-2-(3-methyl-

6-oxo-5,6-dihydropyridazin-1(4H)-yl)acetamide and 2-((4-acetyl-5-(2,4-dichlorophenyl)-4,5-

dihydro-1,3,4-oxadiazol-2-yl)methyl)-6-methyl-4,5-dihydropyridazin-3(2H)-one were

synthesized (Figure). The structures of the target compounds were elucidated by IR, 1HNMR,

and mass spectrometry.

According to the antimycobacterial activity results, our lead compound (2,4-dichlorophenyl

substituted N-acylhydrazone derivative) is still the most active compound among the designed

compounds against M. tuberculosis H37Rv.

The results suggested that some of N'-(substitutedbenzylidene)-2-(3-methyl-6-oxo-5,6-

dihydropyridazin-1(4H)-yl)acetohydrazide derivatives could be potential antimycobacterial

agents against TB.

Acknowledgements

We thank to Dharmarajan Sriram and Perumal Yogeeswari for antimycobacterial activity

studies. This study was funded by Scientific Research Projects Coordination Unit of

Hacettepe University (Grant number: 0801301003).

Keywords: Antimycobacterial activity, tuberculosis, pharmaceutical chemistry