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New Insights into the Structural Requirements of Isatin-Derived Pro-Apoptotic Agents against Acute Myeloid Leukemia

مؤلف البحث
Ahmed K Hamdy, Takashi Sakamoto, Tsugumasa Toma, Masaharu Sakamoto, Mohammed AS Abourehab, Masami Otsuka, Mikako Fujita, Hiroshi Tateishi, Mohamed O Radwan
تاريخ البحث
مجلة البحث
Pharmaceuticals
الناشر
MDPI
عدد البحث
Volume 15, Issue 12
موقع البحث
https://scholar.google.com/scholar?oi=bibs&cluster=14498246465465140847&btnI=1&hl=en
سنة البحث
2022
المشارك في البحث
صفحات البحث
1579
ملخص البحث

Searching for bioactive compounds within the huge chemical space is like trying to find a needle in a haystack. Isatin is a unique natural compound which is endowed with different bio-pertinent activities, especially in cancer therapy. Herein, we envisaged that adopting a hybrid strategy of isatin and α,β-unsaturated ketone would afford new chemical entities with strong chemotherapeutic potential. Of interest, compounds 5b and 5g demonstrated significant antiproliferative activities against different cancer genotypes according to NCI-60 screening. Concomitantly, their IC50 against HL-60 cells were 0.38 ± 0.08 and 0.57 ± 0.05 µM, respectively, demonstrating remarkable apoptosis and moderate cell cycle arrest at G1 phase. Intriguingly, an impressive safety profile for 5b was reflected by a 37.2 times selectivity against HL-60 over PBMC from a healthy donor. This provoked us to further explore their mechanism of action by in vitro and in silico tools. Conclusively, 5b and 5g stand out as strong chemotherapeutic agents that hold clinical promise against acute myeloid leukemia.