A novel sulfamethoxazole derivative as an inhibitory agent against HSP70: A combination of computational with in vitro studies

Moghaddam, Vaha Akbary; Kasmaeifar, Vesal; Mahmoodi, Zainab; Ghafouri, Hossein; Saberi, Omid; Mohammadi, Asadollah

doi:10.1016/j.ijbiomac.2021.08.128

Cited by 13 publications

(8 citation statements)

References 90 publications

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“…Zm-093 was isolated by recrystallization. NMR and FT-IR (Supplementary Figure 1 and 2) spectroscopy confirmed the structure of the obtained azo dye [25].…”

Section: Synthesis Of Azo Compounds Based On 2-amino-5-mercapto-134-t...supporting

confidence: 53%

The Combined Effects of Doxorubicin and a Novel Sulfonamide Derivative on Inducing Apoptosis in a Breast Cancer Cell Line (MCF-7)

Pedarpour,

Zarei,

Mahmoodi

et al. 2024

Preprint

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Chemical combinations are believed to reduce drug toxicity, delay cancer cell growth, and achieve enhanced efficacy compared with single active drugs. This research investigated the synergistic effect of DOX and Zm-093, a new sulfonamide derivative, on improving the potential for inducing apoptosis in breast cancer (BC) cell lines. First, the Zm-093 compound was synthesized and its structure was confirmed by FT-IR and NMR. Then, the IC50 values for DOX and Zm-093 were calculated to be 1.21 and 51.24 μM, respectively. To investigate the synergistic effect, Compusyn software was utilized to calculate the combination index (CI). Different methods, including western blotting, flow cytometry, and TUNEL, were used to evaluate the potential synergistic effects of these compounds on inducing apoptosis in MCF-7 cells. Combining the indexes obtained at all concentrations revealed synergistic results. The proapoptotic proteins Bax, tBid, and caspase-3, however, increased 2.4, 3.3, and 5.7 times more than those in the control group. Flow cytometry analysis and the TUNEL method in cells treated with DOX and Zm-093 showed that apoptosis was significantly higher than in other groups. The results confirmed the synergistic effect of DOX and ZM-093 on apoptotic factors expression in MCF-7 cells.

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“…Zm-093 was isolated by recrystallization. NMR and FT-IR (Supplementary Figure 1 and 2) spectroscopy confirmed the structure of the obtained azo dye [25].…”

Section: Synthesis Of Azo Compounds Based On 2-amino-5-mercapto-134-t...supporting

confidence: 53%

The Combined Effects of Doxorubicin and a Novel Sulfonamide Derivative on Inducing Apoptosis in a Breast Cancer Cell Line (MCF-7)

Pedarpour,

Zarei,

Mahmoodi

et al. 2024

Preprint

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“…7 . The darkest red color indicates the most electron-rich region, capable of acting as one of the best hydrogen bond acceptors, whereas the darkest blue color represent the site which is the most sensitive towards nucleophilic attacks [ 37 ]. As can be seen in Fig.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, in vitro biological evaluation and molecular modelling of new 2-chloro-3-hydrazinopyrazine derivatives as potent acetylcholinesterase inhibitors‏ on PC12 cells

et al. 2022

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Background The loss of cholinergic neurotransmission in Alzheimer's disease (AD) patients' brain is accompanied by a reduced concentration of Acetylcholine (ACh) within synaptic clefts. Thus, the use of acetylcholinesterase inhibitors (AChEIs) to block the cholinergic degradation of ACh is a promising approach for AD treatment. In the present study, a series of 2-chloro-3-hydrazinopyrazine derivatives (CHP1-5) were designed, synthesized, and biologically evaluated as potential multifunctional anti-AD agents. Methods In addition, the chemical structures and purity of the synthesized compounds were elucidated through using IR, 1H and 13C NMR, and elemental analyses. Further, the intended compounds were assessed in vitro for their AChE inhibitory and neuroprotective effects. Furthermore, DPPH, FRAP and ABTS assays were utilized to determine their antioxidant activity. The statistical analysis was performed using one-way ANOVA. Results Based on the results, CHP4 and CHP5 exhibited strong AChE inhibitory effects with the IC50 values of 3.76 and 4.2 µM compared to the donepezil (0.53 µM), respectively. The study examined the effect and molecular mechanism of CHP4 on the Ab1–42-induced cytotoxicity in differentiated PC12 cells. At concentrations of 0–100 μM, CHP4 was non-toxic in PC12. Additionally, Ab1–42 significantly stimulated tau hyperphosphorylation and induced differentiated PC12 cell death. Further, CHP4 resulted in diminishing the Ab1–42-induced toxicity in PC12 cell significantly. CHP4 at 30 μM concentration significantly increased the Ab1–42-induced HSP70 expression and decreased tau hyperphosphorylation. Conclusions According to the results of our studies CHP4 can be considered as safe and efficient AChEI and employed as a potential multifunctional anti-AD agent.

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“…Currently, SP2/0 cells are used as host cells for the production of mAbs such as Abciximab, Basiliximab, Canakinumab, Cetuximab, and Infliximab [ 1 ], as well as Golimumab and Ustekinumab [ 4 ]. Under stressful conditions, cells can protect themselves by inducing heat shock protein (HSP) expression, thereby increasing their chances of survival [ 5 ]. In bioreactors, cellular stress can lead to programmed cell death, as observed in various studies.…”

Section: Introductionmentioning

confidence: 99%

Induction of heat shock protein expression in SP2/0 transgenic cells and its effect on the production of monoclonal antibodies

Jaffaraghaei,

Ghafouri,

Vaziri

et al. 2024

PLoS ONE

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The objective of the current investigation was to evaluate the induction of heat shock proteins (HSPs) in SP2/0 transgenic cells and the effect of these proteins on the production of monoclonal antibodies (mAbs). The SP2/0 cell line expressing the PSG-026 antibody, a biosimilar candidate of golimumab, the culture parameters, and the target protein expression were not justified for industrial production and were used for the experiments. Paracetamol and heat shock were used as chemical and physical inducers of HSPs, respectively. The results showed that paracetamol and heat shock increased the expression of HSP70 and HSP27 at the mRNA and protein levels. The expression of HSPs was greater in paracetamol-treated cells than in heat shock-treated cells. Paracetamol treatment at concentrations above 0.5 mM significantly reduced cell viability and mAb expression. However, treatment with 0.25 mM paracetamol results in delayed cell death and increased mAb production. Heat shock treatment at 45°C for 30 minutes after enhanced mAb expression was applied after pre-treatment with paracetamol. In bioreactor cultures, pretreatment of cells with paracetamol improved cell viability and shortened the lag phase, resulting in increased cell density. The production of mAbs in paracetamol-treated cultures was markedly greater than that in the control. Analysis of protein quality and charge variants revealed no significant differences between paracetamol-treated and control cultures, indicating that the induction of HSPs did not affect protein aggregation or charge variants. These findings suggest that inducing and manipulating HSP expression can be a valuable strategy for improving recombinant protein production in biopharmaceutical processes.

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A novel sulfamethoxazole derivative as an inhibitory agent against HSP70: A combination of computational with in vitro studies

Cited by 13 publications

References 90 publications

The Combined Effects of Doxorubicin and a Novel Sulfonamide Derivative on Inducing Apoptosis in a Breast Cancer Cell Line (MCF-7)

The Combined Effects of Doxorubicin and a Novel Sulfonamide Derivative on Inducing Apoptosis in a Breast Cancer Cell Line (MCF-7)

Synthesis, in vitro biological evaluation and molecular modelling of new 2-chloro-3-hydrazinopyrazine derivatives as potent acetylcholinesterase inhibitors‏ on PC12 cells

Induction of heat shock protein expression in SP2/0 transgenic cells and its effect on the production of monoclonal antibodies

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