The Mechanism of Anti-Tumor Activity of 6-Morpholino- and 6-Amino-9-Sulfonylpurine Derivatives on Human Leukemia Cells

Leventić, Marijana; Opačak-Bernardi, Teuta; Rastija, Vesna; Matić, Josipa; Pavlović Saftić, Dijana; Ban, Željka; Žinić, Biserka; Glavaš-Obrovac, Ljubica (2023) The Mechanism of Anti-Tumor Activity of 6-Morpholino- and 6-Amino-9-Sulfonylpurine Derivatives on Human Leukemia Cells. Molecules, 28 (16). ISSN 1420-3049

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Abstract

The aim of this study was to explore the mechanism of antitumor effect of (E)-6-morpholino-9-(styrylsulfonyl)-9H-purine (6-Morpholino-SPD) and (E)-6-amino-9-(styrylsulfonyl)-9H-purine (6-Amino-SPD). The effects on apoptosis induction, mitochondrial potential, and accumulation of ROS in treated K562 cells were determined by flow cytometry. The RT-PCR method was used to measure the expression of Akt, CA IX, caspase 3, and cytochrome c genes, as well as selected miRNAs. Western blot analysis was used to determine the expression of Akt, cytochrome c, and caspase 3. The results demonstrate the potential of the tested derivatives as effective antitumor agents with apoptotic-inducing properties. In leukemic cells treated with 6-Amino-SPD, increased expression of caspase 3 and cytochrome c genes was observed, indicating involvement of the intrinsic mitochondrial pathway in the induction of apoptosis. Conversely, leukemic cells treated with 6-Morpholino-SPD showed reduced expression of these genes. The observed downregulation of miR-21 by 6-Morpholino-SPD may contribute to the induction of apoptosis and disruption of mitochondrial function. In addition, both derivatives exhibited increased expression of Akt and CA IX genes, suggesting activation of the Akt/HIF pathway. However, the exact mechanism and its relations to the observed overexpression of miR-210 need further investigation. The acceptable absorption and distribution properties predicted by ADMET analysis suggest favorable pharmacokinetic properties for these derivatives.

Item Type:	Article
Uncontrolled Keywords:	N-9-sulfonylpurines; leukemia cells; anti-tumor; apoptosis; gene expression; miRNA expression; ADMET properties
Subjects:	NATURAL SCIENCES > Chemistry NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Višenamjensko očitavanje DNA/RNA sekundarne strukture molekularnim kemijskim senzorima-DNA/RNA-MolSense Ivo Piantanida; Carsten Schmuck; Tamara Šmidlehner IP-2013-11-1477 HRZZ
Depositing User:	Josipa Karadžole
Date Deposited:	25 Mar 2026 11:23
URI:	http://fulir.irb.hr/id/eprint/11469
DOI:	10.3390/molecules28166136

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