Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile

A series of twelve novel hybrids of cinnamic acid and thiocarbohydrazones were designed, synthesized in high yield using a simple coupling strategy via acid chlorides, and evaluated for their impact against Mycobacterium tuberculosis (Mtb) and cancer cells survival. Among them, compound 3 demonstrat...

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Autores principales:	Mohamed H. Assaleh, Snezana K. Bjelogrlic, Nevena Prlainovic, Ilija Cvijetic, Aleksandra Bozic, Irena Arandjelovic, Dragana Vukovic, Aleksandar Marinkovic
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Cinnamic acid hydrazides Mycobacterium tuberculosis Anti-mycobacterial Anti-cancer Hepatotoxicity Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/6b03d804b615461e9396edd3aa2fc120
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spelling	oai:doaj.org-article:6b03d804b615461e9396edd3aa2fc1202021-11-14T04:31:29ZAntimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile1878-535210.1016/j.arabjc.2021.103532https://doaj.org/article/6b03d804b615461e9396edd3aa2fc1202022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1878535221005475https://doaj.org/toc/1878-5352A series of twelve novel hybrids of cinnamic acid and thiocarbohydrazones were designed, synthesized in high yield using a simple coupling strategy via acid chlorides, and evaluated for their impact against Mycobacterium tuberculosis (Mtb) and cancer cells survival. Among them, compound 3 demonstrated strong anti-Mtb activity by reducing bacilli survival for>90 % in all three treated Mtb isolates, whereas isoniazid and rifampicin did not. Moreover, compound 3 didn’t affect vitality of HepG-2 cells, implying on advantageous hepatotoxicity profile compared to current therapeutic options for tuberculosis. Compounds 2a and 3b displayed as strong inducers of apoptosis in A549 cells, both activating intrinsic caspase pathway and cell cycle arrest at the G0/G1 phase. Subsequent analyses disclosed differences in their activities, where 3b has ability to induce production of mitochondrial superoxide anions, while 2a significantly inhibited cellular mobility. More importantly, 3b considerably affected viability of HepG-2 and HaCaT cells, whereas 2a had moderate impact only on the later. Molecular modeling studies indicated high permeability and good absorption through the human intestine, and moderate aqueous solubility with poor blood–brain barrier permeability. In summary, our results reveal that novel compounds 3 and 2a represent promising agents for tuberculosis and cancer treatment, respectively, indicating that further investigation needs to be performed to clarify the mechanisms of their anti-Mtb and anticancer activity.Mohamed H. AssalehSnezana K. BjelogrlicNevena PrlainovicIlija CvijeticAleksandra BozicIrena ArandjelovicDragana VukovicAleksandar MarinkovicElsevierarticleCinnamic acid hydrazidesMycobacterium tuberculosisAnti-mycobacterialAnti-cancerHepatotoxicityChemistryQD1-999ENArabian Journal of Chemistry, Vol 15, Iss 1, Pp 103532- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cinnamic acid hydrazides Mycobacterium tuberculosis Anti-mycobacterial Anti-cancer Hepatotoxicity Chemistry QD1-999
spellingShingle	Cinnamic acid hydrazides Mycobacterium tuberculosis Anti-mycobacterial Anti-cancer Hepatotoxicity Chemistry QD1-999 Mohamed H. Assaleh Snezana K. Bjelogrlic Nevena Prlainovic Ilija Cvijetic Aleksandra Bozic Irena Arandjelovic Dragana Vukovic Aleksandar Marinkovic Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile
description	A series of twelve novel hybrids of cinnamic acid and thiocarbohydrazones were designed, synthesized in high yield using a simple coupling strategy via acid chlorides, and evaluated for their impact against Mycobacterium tuberculosis (Mtb) and cancer cells survival. Among them, compound 3 demonstrated strong anti-Mtb activity by reducing bacilli survival for>90 % in all three treated Mtb isolates, whereas isoniazid and rifampicin did not. Moreover, compound 3 didn’t affect vitality of HepG-2 cells, implying on advantageous hepatotoxicity profile compared to current therapeutic options for tuberculosis. Compounds 2a and 3b displayed as strong inducers of apoptosis in A549 cells, both activating intrinsic caspase pathway and cell cycle arrest at the G0/G1 phase. Subsequent analyses disclosed differences in their activities, where 3b has ability to induce production of mitochondrial superoxide anions, while 2a significantly inhibited cellular mobility. More importantly, 3b considerably affected viability of HepG-2 and HaCaT cells, whereas 2a had moderate impact only on the later. Molecular modeling studies indicated high permeability and good absorption through the human intestine, and moderate aqueous solubility with poor blood–brain barrier permeability. In summary, our results reveal that novel compounds 3 and 2a represent promising agents for tuberculosis and cancer treatment, respectively, indicating that further investigation needs to be performed to clarify the mechanisms of their anti-Mtb and anticancer activity.
format	article
author	Mohamed H. Assaleh Snezana K. Bjelogrlic Nevena Prlainovic Ilija Cvijetic Aleksandra Bozic Irena Arandjelovic Dragana Vukovic Aleksandar Marinkovic
author_facet	Mohamed H. Assaleh Snezana K. Bjelogrlic Nevena Prlainovic Ilija Cvijetic Aleksandra Bozic Irena Arandjelovic Dragana Vukovic Aleksandar Marinkovic
author_sort	Mohamed H. Assaleh
title	Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile
title_short	Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile
title_full	Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile
title_fullStr	Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile
title_full_unstemmed	Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile
title_sort	antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/6b03d804b615461e9396edd3aa2fc120
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Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile

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