VCOM Louisiana Research Day Program Book 2024

Biomedical Research: Section 2

Anthony Agu, Atchimnaidu Siriki, PhD; Gholamian Moghaddam Ali, Siva Murru, PhD University of Louisiana Monroe 19 SYNTHESIS OF PYRAZOLONE DERIVATIVES VIA SONOGASHIRA AND HECK COUPLING FOR EVALUATION OF THEIR ANTICANCER ACTIVITY AGAINST COLORECTAL CANCER CELLS

Background: Colorectal cancer (CRC) is the second leading cause of death from cancer in the world. Due to its high incidence and mortality rate worldwide, the global burden of CRC is expected to increase by 60% to more than 2.2 million new cases and 1.1 million deaths by 2030. Even though the treatment outcomes for people with early-onset CRC have been improving, there is no effective treatment for advanced CRC patients, and only 12% of overall five-year survival rates. Accordingly, there is a high need for the development of new anticancer drugs that possess curative efficacy, high selectivity, and lower toxicity. Recently, we have made noteworthy strides in the realm of small-molecule anticancer agents by crafting compounds rooted in pyrazoles and pyrazolones. Objective: Pyrazole and Pyrazolone derivatives attracted huge attention in recent years as synthetic scaffolds in combinatorial and medicinal chemistry. Also, they have been found to have a broad spectrum of pharmacology properties. Incentivized by these findings we proceeded to synthesize pyrazole and pyrazolone derivatives. In the study, we evaluated the activity of synthesized pyrazoles and pyrazolone derivatives as potent anti-CRC compounds. Furthermore, we are currently

studying potential molecular mechanisms underlying the effects of these compounds on CRC cells. Methods: Guided by promising preliminary data regarding their anticancer properties, our research endeavors have led to the synthesis of a library of pyrazolone derivatives via Sonogashira and Heck cross-coupling reactions using conventional methods. We subjected all synthesized compounds to MTT assays against colorectal cancer cell lines, such as Widr and HCT-116, revealing a selection of potent compounds exhibiting favorable IC50 values. Results: Our lab successfully developed a diverse array of small-molecule compounds via Sonogashira and Heck cross-coupling reactions. The structure of each compound was confirmed using HRMS. Afterward, we screened these compounds against CRC cancer cell lines (HCT 116 and WiDr) using the MTT assay. According to our screening results, we identified some highly potent and active compounds, these active compounds were later tested on normal colon cells CCD 841 Con to ascertain their selectivity. Conclusions: We successfully developed cross-coupling approaches for the synthesis of

diverse pyrazolone molecular hybrids. Among the compounds tested, we have identified a set of potent compounds against CRC cells. Subsequently, we will carry out mechanistic studies to identify possible molecular targets of these compounds.

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