New Insights into the Structural Requirements of Isatin-derived Pro-apoptotic Agents against Acute Myeloid Leukemia

Ahmed K. Hamdy; Takashi Sakamoto; Tsugumasa Toma; Masaharu Sakamoto; Mohammed A.S Abourehab; Masami Otsuka; Mikako Fujita; Hiroshi Tateishi; Mohamed O. Radwan

doi:10.20944/preprints202211.0509.v1

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preprints.org > chemistry and materials science > medicinal chemistry > doi: 10.20944/preprints202211.0509.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

New Insights into the Structural Requirements of Isatin-derived Pro-apoptotic Agents against Acute Myeloid Leukemia

Mohammed A.S Abourehab

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Version 1 : Received: 28 November 2022 / Approved: 28 November 2022 / Online: 28 November 2022 (09:59:20 CET)

A peer-reviewed article of this Preprint also exists.

Hamdy, A.K.; Sakamoto, T.; Toma, T.; Sakamoto, M.; Abourehab, M.A.S.; Otsuka, M.; Fujita, M.; Tateishi, H.; Radwan, M.O. New Insights into the Structural Requirements of Isatin-Derived Pro-Apoptotic Agents against Acute Myeloid Leukemia. Pharmaceuticals 2022, 15, 1579. Hamdy, A.K.; Sakamoto, T.; Toma, T.; Sakamoto, M.; Abourehab, M.A.S.; Otsuka, M.; Fujita, M.; Tateishi, H.; Radwan, M.O. New Insights into the Structural Requirements of Isatin-Derived Pro-Apoptotic Agents against Acute Myeloid Leukemia. Pharmaceuticals 2022, 15, 1579.

Abstract

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 biopertinent activities specially 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 assay. Concomitantly, their IC50 against HL-60 cells were 0.38 ± 0.08 and 0.57 ± 0.05, respectively, demonstrating remarkable apoptosis and mod-erate 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 a clinical promise against acute myeloid leukemia.

Keywords

isatin; indolin-2-one; acute myeloid leukemia; apoptosis; ERK1/2; MAPK

Subject

Chemistry and Materials Science, Medicinal Chemistry

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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