Establishment of Physalis alkekengi cell suspension culture: time-dependent behavior of genes related to the steroidal compounds, key enzymes, and physalins under static magnetic field

Article

Author: Hassanpour, Halimeh

Cell suspension culture has the potential to be a valuable source for the bioactive compound productions. In this study, an optimized procedure was established for callus and cell suspension culture of Physalis alkekengi for the first time, and the impact of static magnetic field (SMF, 6 mT) was studied on the high-value metabolic compounds through investigation of signaling molecules and gene expressions at the late log-to-stationary phase. Results showed that the growth regulators of 6-benzyl amino purine (BAP, 1.5 mg^-1 L) and 1-naphthaleneacetic acid (NAA, 0.4 mg^-1 L) induced the highest fresh weight, callus rate, callus index, and total withanolides. Cell suspension culture was established in the liquid MS medium supplied with BAP (1.5 mg^-1 L) and NAA (0.1 mg^-1 L). SMF application decreased slightly the cell growth and viability and enhanced the number of round-shaped cells. The hydrogen peroxide (H₂O₂) and nitric oxide (NO) levels increased at an all-time series after SMF exposure, and their maximum contents were observed after 12 h. A significant alteration of malondialdehyde content was also identified after 12 h of SMF exposure. The expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), 1-deoxyD-xylulose 5-phosphate synthase (DXS), squalene synthase (SQS), sterol Δ7-reductase (DWF5), and C-7,8 sterol isomerase (HYD1) genes was upregulated significantly after 24 and 48 h. An increase in the total withanolides was related to more activity of HMGR and DXS enzymes in SMF-exposed cells and the maximum physalin A (12.8 mg g^-1 DW) and physalin B (1.92 mg g^-1 DW) obtained after 24 h compared to controls. Findings suggest that SMF can play a supportive factor in inducing steroidal compounds in P. alkekengi through modulating H₂O₂ and NO levels and the related-gene expressions.

01 Oct 2024·Future Medicinal Chemistry

New 6-nitro-4-substituted quinazoline derivatives targeting epidermal growth factor receptor: design, synthesis and in vitro anticancer studies

Article

Author: Othman, Aya H ; El-Ashrey, Mohamed K ; Farag, Ayman B ; Abbas, Safinaz E-S. ; Elwaie, Tamer A

Aim: Twenty compounds of 6-nitro-4-substituted quinazolines were synthesized.Materials & methods: The new derivatives were evaluated for their epidermal growth factor receptor (EGFR) inhibitory activity. The most potent derivatives were assessed for their cytotoxicity against colon cancer and lung cancer cells, in addition to normal fibroblast cells.Results & discussion: compound 6c showed a superior to nearly equal cytotoxicity in comparison to gefitinib, it also revealed a good safety profile. Compound 6c caused a cell cycle arrest at G2/M phase in addition to induction of apoptosis. A molecular docking study was conducted on the most active compounds to gain insights of their binding mode in the active site of EGFR enzyme besides ADME prediction of their physicochemical properties and drug likeness profile.

19 Aug 2023·Molecules (Basel, Switzerland)

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

Article

Author: Rastija, Vesna ; Žinić, Biserka ; Pavlović Saftić, Dijana ; Ban, Željka ; Opačak-Bernardi, Teuta ; Glavaš-Obrovac, Ljubica ; Leventić, Marijana ; Matić, Josipa

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.

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