Synthesis and biological evaluation of substituted pyrrolidines and pyrroles as potential anticancer agents

Ji, Jiali; Sajjad, Farrukh; You, Qun; Xing, Dong; Reddy, Alavala Gopi Krishna; Hu, Wenhao; Shen, Dong

doi:10.1002/ardp.202000136

Cited by 13 publications

(12 citation statements)

References 21 publications

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“…Morphologically, AO/PI staining con rmed apoptosis, and detection of PS externalization showed a decrease in the number of living cells and a signi cant increase in the number of apoptotic (early and late) and dead cells after SS13 exposure in colorectal carcinoma cells. These results were consistent with several studies in which time-dependent apoptosis was observed after treatment with pyrrolidine derivates [17,32]. The apoptotic process is associated with reduced MMP and the release of pro-apoptotic proteins, such as cytochrome c, to the cytosol.…”

Section: Discussionsupporting

confidence: 93%

Newly synthesized pyrrolidine analog SS13 induces extrinsic and intrinsic apoptotic pathways in colorectal cancer cells

Nosálová

Kešeľáková

Kello

et al. 2023

Preprint

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Background A series of experiments on colorectal cancer cells (Caco-2 and HCT116) were conducted to provide new information about the antiproliferative and pro-apoptotic effect of newly synthesized (2S,3S,4R)-2-Tridecylpyrrolidine-3,4-diol hydrochloride (SS13). Methods BrdU proliferation and MTT assays were performed to verify the antiproliferative activity and determine the IC50 value. Flow cytometry was used for cell cycle analysis, phosphatidylserine externalization, mitochondrial membrane potential, and casp-3/7 activation. Cleavage of PARP and casp-8, as well as protein levels of Bad, pBad, Bcl-2, pBcl-2, and Bcl-xL were detected by western blot. Gene expression was determined by qRT–PCR. The impact of SS13 on cell migration was monitored by scratch assay. Results SS13 showed the concentration-dependent cytotoxic and antiproliferative effect on both cell lines with IC50: 3.2 ± 0.1 μmol/L - MTT / vs. 6.46 ± 2.84 μmol/L - BrdU for HCT116 and 2.17 ± 1.5 μmol/L – MTT vs. 1.59 ± 0.72 μmol/L BrdU for Caco-2. SS13-induced apoptosis was associated with externalization of phosphatidylserine, reduced MMP, activation of casp-3/7, cleavage of PARP and casp-8, overexpression of TNF-α, FasL, and dysregulation of Bcl-2 family proteins. SS13 induced intrinsic and extrinsic apoptotic pathways in colorectal cancer cells and inhibited their migration potential. Conclusions Newly synthesized pyrrolidine SS13 induced intrinsic and extrinsic apoptotic pathways in colorectal cancer cells and suppressed their migration. Our results suggest that pyrrolidine SS13 may have potential in prevention and treatment of colorectal cancer.

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Section: Discussionsupporting

confidence: 93%

Newly synthesized pyrrolidine analog SS13 induces extrinsic and intrinsic apoptotic pathways in colorectal cancer cells

Nosálová

Kešeľáková

Kello

et al. 2023

Preprint

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“…Moreover, Ji et al found that pyrrole analogues showed a significant proliferation inhibitory effect in 10 different cancer cell lines. Furthermore, pyrrolidine stimulates cell cycle arrest and apoptosis mechanisms in both colorectal carcinoma (HCT116) and leukemia cells (HL60) (Ji et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

PhTAD-Substituted Dihydropyrrole Compounds Regulate Apoptotic Cell Death in MCF-7 Cells

Yazgan

Mesci

Akşahin

et al. 2021

Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi

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Breast cancer is the most common type of cancer amongst women. Apoptosis is known as a programmed cell death and this mechanism induces cancer cell death. Dihydropyrrole compounds contain a heterocyclic structure and these molecules have many biological effects including functioning as antioxidants and anticancer molecules. In this regard, the aim of this research was to investigate how PhTAD-substituted dihydropyrrole compounds affect the expression of apoptotic cell death proteins in the MCF-7 cells. The levels of Bax, Bcl-2, and cleaved caspase-3 proteins in the MCF-7 cells were measured using the ELISA method. The results revealed that CI, CII, CIII, CV, CVII, CVIII, CXI and CXII increased Bax, while CXIII and CXIV markedly decreased Bax. In addition, compounds CI, CII, CIII, CVII, CVIII, CXI and CXII upregulated Bcl2. Conversely, CIV, and CXIV downregulated Bcl2. Moreover, CIV and CXIV increased the Bax/Bcl2 ratio. However, CVIII and CXIII decreased Bax/Bcl2 ratio. In addition, CI, CIV, CIX and CXII treatment increased cleaved caspase-3 in MCF-7 cells compared to the negative control. These findings indicate that the PhTADsubstituted dihydropyrrole derivative molecules induced apoptotic proteins as a potential regulator of cancer cell death.

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“…Also, these molecules exhibit good antibacterial activity. Ji et al [ 117 ] reported ruthenium-catalyzed synthesis and antiproliferation activities of poly substituted pyrrolidines. Among these analogs, only compounds (35 a, b) have shown strong antiproliferation activity with IC 50 —2.9 to 16 μM (Fig.…”

Section: Anticancer Agentsmentioning

confidence: 99%

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

Basha¹,

Basavarajaiah²,

Shyamsunder³

2022

Mol Divers

102

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The chemistry of nitrogen-containing heterocyclic compound pyrrole and pyrrolidine has been a versatile field of study for a long time for its diverse biological and medicinal importance . Biomolecules such as chlorophyll, hemoglobin, myoglobin, and cytochrome are naturally occurring metal complexes of pyrrole. These metal complexes play a vital role in a living system like photosynthesis, oxygen carrier, as well storage, and redox cycling reactions. Apart from this, many medicinal drugs are derived from either pyrrole, pyrrolidine, or by its fused analogs. This review mainly focuses on the therapeutic potential of pyrrole, pyrrolidine, and its fused analogs, more specifically anticancer, anti-inflammatory, antiviral, and antituberculosis. Further, this review summarizes more recent reports on the pyrrole, pyrrolidine analogs, and their biological potential. Graphical Abstract

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Synthesis and biological evaluation of substituted pyrrolidines and pyrroles as potential anticancer agents

Cited by 13 publications

References 21 publications

Newly synthesized pyrrolidine analog SS13 induces extrinsic and intrinsic apoptotic pathways in colorectal cancer cells

Newly synthesized pyrrolidine analog SS13 induces extrinsic and intrinsic apoptotic pathways in colorectal cancer cells

PhTAD-Substituted Dihydropyrrole Compounds Regulate Apoptotic Cell Death in MCF-7 Cells

Therapeutic potential of pyrrole and pyrrolidine analogs: an update

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