Assessment of antioxidant capacity in vitro of synthetic compounds containing a 4-(substituted phenyl)-/4-(diphenylmethyl)piperazin-1-yl structural motif, promising as cardiovascular drugs, or antimycobacterial agents

Authors: Alena Laura Merz 1    Lucia Hudecová 1    Maria Pecháčová 2    Gustáv Kováč 1    Ivan Malík 1,2   
1 Institute of Chemistry, Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Slovak Medical University, Limbová 12, 833 03 Bratislava, Slovak Republic    2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32 Bratislava, Slovak Republic   
Year: 2021
Section: Clinical studies and applied experimental research in medicine
Abstract No.: 2172
ISBN: ISBN 978-80-972360-7-6

The biological significance of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) is rather complex and paradoxical. Elevated levels of ROS have commonly been implicated in a variety of pathological conditions and diseases, including cardiovascular diseases, cancer, inflammation, and neurodegenerative diseases as well. Nevertheless, ROS and RNS are generated immediately after the recognition of any invading foreign pathogens such as viruses, or bacteria to destroy them. 

Mycobacterium tuberculosis is a causative agent of human tuberculosis, an ancient disease, which is one of the major leading causes of infectious deaths globally. During a phagocytosis process, M. tuberculosis evades the host defense mechanisms to prolong their existence in humans. Activation of pro-inflammatory cytokines by ROS/RNS in macrophages during phagocytosis is important in eliminating the pathogen by host immunity. However, the mycobacterium has found ways to downregulate the inflammatory response and ROS/RNS produced in macrophages.

In the current research, a series of hybrid compounds, promising as cardiovascular/antimycobacterial agents, which contain a phenylcarbamoyloxy moiety, connecting 2-hydroxypropan-1,3-diyl chain and 4-(substituted phenyl)-/4-(diphenylmethyl)piperazin-1-yl group was in vitro evaluated in order to inspect their potential to reduce a DPPH radical. 

Moderate antioxidant capacity of 1-[2-hydroxypropyl-3-(phenylcarbamoyloxy)]-4-(4-methoxyphenyl)piperazin-1-ium chloride (6g) has been detected and might be the favourable feature if focusing on this molecule as an effective cardiovascular drug.

On the other hand, 1-[2-hydroxypropyl-3-(phenylcarbamoyloxy)]-(3,4-dichlorophenyl)piperazin-1-ium chloride (6b) might supposed to be an effective anti-TB agent in terms of its very suitable structural arrangement and selection of substituents within a basic fragment. Among the currently screened derivatives, the compound 6b showed the lowest potential to reduce the radical, thus, this property would not weaken its assumed anti-TB activity.

None of the assessed synthetic compounds have proved antioxidant capacity of reference Trolox molecule.

Keywords: ROS, RNS, cardiovascular diseases, tuberculosis, cardiovascular drugs, antimycobacterial agents, antioxidant capacity, piperazine compounds with aromatic rings.