1H-1,2,3-triazole embedded Isatin-Benzaldehyde-bis(heteronuclearhydrazones): design, synthesis, antimycobacterial, and cytotoxic evaluation.

Sharma, B; Kumar, S; Preeti,; Johansen, MD; Kremer, L; Kumar, V

1H-1,2,3-triazole embedded Isatin-Benzaldehyde-bis(heteronuclearhydrazones): design, synthesis, antimycobacterial, and cytotoxic evaluation.

Sharma, B Kumar, S Preeti, Johansen, MD Kremer, L Kumar, V

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Publisher:: Wiley
Publication Type:: Journal Article
Citation:: Chemical Biology and Drug Design, 2022, 99, (2), pp. 301-307
Issue Date:: 2022

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Field	Value	Language
dc.contributor.author	Sharma, B
dc.contributor.author	Kumar, S
dc.contributor.author	Preeti,
dc.contributor.author	Johansen, MD
dc.contributor.author	Kremer, L
dc.contributor.author	Kumar, V
dc.date.accessioned	2022-12-14T01:49:09Z
dc.date.available	2021-10-30
dc.date.available	2022-12-14T01:49:09Z
dc.date.issued	2022
dc.identifier.citation	Chemical Biology and Drug Design, 2022, 99, (2), pp. 301-307
dc.identifier.issn	1747-0277
dc.identifier.issn	1747-0285
dc.identifier.uri	http://hdl.handle.net/10453/164387
dc.description.abstract	Rapid growth of global drug-resistant tuberculosis and urgent requirement for short treatment regimens is stimulating the need for discovery of new TB drugs. In this work, we report the design, synthesis and in vitro antimycobacterial evaluation of a library of isatin-derived bis(heteronuclear hydrazones). Evaluation results revealed that the inclusion of isoniazid core into 1H-1,2,3-triazole tethered isatin-benzaldehydes improved the antimycobacterial activity on tuberculosis mc<sup>2</sup> 6230 strain and significantly reduced the cytotoxicity against Vero cells. However, the introduction of semicarbazones/thiosemicarbazones or pyrazine-2-carbohydrazide produced the opposite effects. The compounds with isoniazid and polar-donating groups at the C-5 position of isatin emerged as the most promising conjugates with MIC<sub>99</sub> = 0.36 µg/ml. The most active compounds were non-cytotoxic to Vero cells (IC<sub>50</sub> >100 µg/ml) with selectivity indices >277.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Wiley
dc.relation.ispartof	Chemical Biology and Drug Design
dc.relation.isbasedon	10.1111/cbdd.13984
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0601 Biochemistry and Cell Biology
dc.subject.classification	Biophysics
dc.subject.classification	Medicinal & Biomolecular Chemistry
dc.subject.mesh	Animals
dc.subject.mesh	Antitubercular Agents
dc.subject.mesh	Benzaldehydes
dc.subject.mesh	Chlorocebus aethiops
dc.subject.mesh	Drug Design
dc.subject.mesh	Hydrazones
dc.subject.mesh	Isatin
dc.subject.mesh	Microbial Sensitivity Tests
dc.subject.mesh	Mycobacterium tuberculosis
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Triazoles
dc.subject.mesh	Vero Cells
dc.subject.mesh	Vero Cells
dc.subject.mesh	Animals
dc.subject.mesh	Mycobacterium tuberculosis
dc.subject.mesh	Benzaldehydes
dc.subject.mesh	Hydrazones
dc.subject.mesh	Triazoles
dc.subject.mesh	Isatin
dc.subject.mesh	Antitubercular Agents
dc.subject.mesh	Microbial Sensitivity Tests
dc.subject.mesh	Structure-Activity Relationship
dc.subject.mesh	Drug Design
dc.subject.mesh	Chlorocebus aethiops
dc.title	1H-1,2,3-triazole embedded Isatin-Benzaldehyde-bis(heteronuclearhydrazones): design, synthesis, antimycobacterial, and cytotoxic evaluation.
dc.type	Journal Article
utslib.citation.volume	99
utslib.location.activity	England
utslib.for	0601 Biochemistry and Cell Biology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2022-12-14T01:49:08Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	99
utslib.citation.issue	2

Abstract:

Rapid growth of global drug-resistant tuberculosis and urgent requirement for short treatment regimens is stimulating the need for discovery of new TB drugs. In this work, we report the design, synthesis and in vitro antimycobacterial evaluation of a library of isatin-derived bis(heteronuclear hydrazones). Evaluation results revealed that the inclusion of isoniazid core into 1H-1,2,3-triazole tethered isatin-benzaldehydes improved the antimycobacterial activity on tuberculosis mc² 6230 strain and significantly reduced the cytotoxicity against Vero cells. However, the introduction of semicarbazones/thiosemicarbazones or pyrazine-2-carbohydrazide produced the opposite effects. The compounds with isoniazid and polar-donating groups at the C-5 position of isatin emerged as the most promising conjugates with MIC₉₉ = 0.36 µg/ml. The most active compounds were non-cytotoxic to Vero cells (IC₅₀ >100 µg/ml) with selectivity indices >277.

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http://hdl.handle.net/10453/164387