Synthesis and In Vitro Evaluation of Novel 1,2,3,4-Tetrahydroisoquinoline Derivatives as Potent Antiglioma Agents
Renukadevi Patil, Amira Hosni-Ahmed, Terreia S. Jones, Shivaputra A. Patil, Likeselam B. Asres, Xiangdi Wang, Ryan C. Yates, Eldon E. Geisert and Duane D. Miller
Affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Egypt.
Keywords: Antiglioma activity, EDL-155 analogs, glioblastoma multiforme (GBM), tetrahydroisoquinoline (THI).
Glioblastoma Multiforme (GBM) continues to demand improved chemotherapeutic solutions. In order to discover novel
chemotherapeutic agents for GBM, we identified novel tetrahydroisoquinoline (THI) analogs as antiglioma agents. The present study
reports the design, synthesis and in vitro evaluation of new THI derivatives in four established human glioma cell lines (T98, U87, LN18
and A172). Our structure activity relationship (SAR) studies revealed that the important modification of the carbon linker between the
biphenyl and THI ring yielded EDL-360 (12) as a potent antiglioma agent (LN18; IC50: 5.42 ±0.06 μM) and is considered to be our new
lead drug candidate for further preclinical studies.
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