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1.
BMC Complement Med Ther ; 23(1): 69, 2023 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-36870998

RESUMO

BACKGROUND: Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells. METHODS: We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3. RESULTS: Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death. CONCLUSION: This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.


Assuntos
Neoplasias Hepáticas , MicroRNAs , Humanos , Sorafenibe , Simulação de Acoplamento Molecular , Epigênese Genética
2.
RSC Adv ; 12(48): 31180-31185, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36349028

RESUMO

Three homopolymers were successfully synthesized by direct CH-CH arylation polymerization of thieno[3,4-c]pyrrole-4,6-dione or pyromellitic diimide derivatives affording highly purified polymers with high molecular weights (43.0-174.7 K). Thieno[3,4-c]pyrrole-4,6-dione and pyromellitic diimide derivatives are considered as electron-withdrawing units. The synthesized homopolymers P1, P2, and P3 showed band gaps in the range of 2.13-2.08 eV, respectively. The electron mobilities of the three homopolymers have been investigated. The thin film transistor for P1 prepared by the eutectic-melt-assisted nanoimprinting method achieved an electron mobility of 2.11 × 10-3 cm2 s-1 V-1. Based on the obtained results, the synthesized polymers can be used as potential electron acceptors in solar cell applications.

3.
Nucleosides Nucleotides Nucleic Acids ; 22(9): 1737-46, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14533878

RESUMO

Treatment of piperidinium salts of dihydropyridinethiolates 3 with glycosyl bromides 4 in dry acetone provides a convenient and high yielding synthesis of 1,4-dihydro-3-cyanopyridine thioglycosides 5. The structures of 5 were confirmed by oxidation as well as by 1H NMR and 13C NMR spectral analysis.


Assuntos
Fármacos Anti-HIV/síntese química , Di-Hidropiridinas/síntese química , Tioglicosídeos/síntese química , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Di-Hidropiridinas/farmacologia , HIV-1/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Tioglicosídeos/química
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