Synthesis and biological evaluations of novel pyrazinoic acid derivatives as anticancer agents

Abstract

Pyrazinoic acid or pyrazine-2-carboxylic acid (PA), due to its nitrogenous heteroaromatic ring, can be explored as an anticancer agent. Here, a series of twenty novels PA derivatives have been synthesized and characterized using IR, NMR, and mass spectrums. Their cytotoxic activity was evaluated against three different cancer cell lines, including lung (A549), breast (MCF-7), and colon (HT-29). P16, the most potent compound, showed moderate cytotoxicity with IC 50 of 6.11 μM, 10.64 μM, and 14.92 μM, against the A549, MCF-7, and HT-29 cell lines, respectively. Furthermore, the effect of this compound against MRC5 as a non-tumoral lung cell line, exhibited a selectivity index of 9.02. The apoptotic induction activity of P16 was also performed on the A549 cell line. The results showed that as the concentration of the compound increases (from 3 to 6 μM), the percentage of induction of apoptosis increases from 8.54% to 72.4%. Electrophoretic gel mobility shift assays showed that P16 was also able to ROS induce DNA cleavage in the presents of H 2 O 2 (1.0 mM) in dose-dependent manner. Molecular docking was also applied to anticipate the binding locations and the binding of the synthesized compound with Bcl-2 apoptosis regulator and DNA as their proposed targets.

Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs

“…Pyrazine-2-carboxylic acid (PA), due to its heteroaromatic ring, can be explored as an anticancer agent. In a very recent paper [ 122 ], a series of twenty novels PA derivatives were synthesized using the Passerini reaction. Their cytotoxic activity was evaluated against three different cancer cell lines, including lung (A549), breast (MCF-7) and colon (HT-29); cisplatin was used as a reference drug.…”

Exploring Anticancer Potential: Synthesis and Assessment of the Biological Activity of Novel Synthesized Pyrazinoic Acid Derivatives

“…[6,7] The anticancer activity of DNA-interfering com-pounds could be through binding to the DNA and/or enzymes necessary for appropriate DNA functions, leading to changes in cellular response and cell apoptosis. [8,9] Consequently, it is crucial to investigate the interactions between these compounds and DNA in order to gain a deeper understanding of their molecular mechanisms of action. This understanding can aid in predicting the interactions of structurally similar analogs and facilitate the identification of potential therapeutic candidates.…”

“…DNA‐interfering compounds possess anticancer activity via diverse approaches [6,7] . The anticancer activity of DNA‐interfering compounds could be through binding to the DNA and/or enzymes necessary for appropriate DNA functions, leading to changes in cellular response and cell apoptosis [8,9] . Consequently, it is crucial to investigate the interactions between these compounds and DNA in order to gain a deeper understanding of their molecular mechanisms of action.…”

“…Pyrazinoic acid or pyrazine‐2‐carboxylic acid (PA) is the metabolite product of pyrazinamide that can play an anticancer role due to its heterocyclic pyrazine ring. The PA showed a wide range of biological activities, such as antibacterial activity against mycobacterium tuberculosis in humans, [14] antiviral, [15] antifungal, [16] and antitumor activity [9] . The synthesized PA derivatives showed a wide variety of pharmacological properties [17] .…”

Efficient synthesis and biological evaluation of some new series of pyridine derivatives: Promising and potent new class of anticancer agents

“…Overall, 28.4 million new cancer cases are expected in 2040, a 47% increase from 19.3 million in 2020, assuming local rates remain stable in 2020. [ 1–3 ] Heterocyclic systems that containing nitrogen have a great importance because of their vital role in biological systems [ 4 ] recently, different heterocyclic nitrogen rings have shown very complex biological properties that making them one of the most important groups in the medicinal chemistry molecules. [ 5 ] Among these heterocycles, pyridine is the simplest one of the azine type.…”