Discovery of aromatic amides with triazole-core as potent reversal agents against P-glycoprotein-mediated multidrug resistance.

Discovery of aromatic amides with triazole-core as potent reversal agents against P-glycoprotein-mediated multidrug resistance. Bioorg Chem. 2019 Jun 21;90:103083 Authors: Qiu Q, Zhu J, Chen Q, Jiang Z, Xu J, Jiang X, Huang W, Liu Z, Ye J, Xu X Abstract P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major impediment for clinical cancer therapy. 19 novel aromatic amides with triazole-core as MDR reversal agents were designed and synthesized via click chemistry to reverse MDR. Among them, compound 42 was identified as the most promising candidate with high potency (EC50 = 78.1 ± 5.4 nM), low cytotoxity (SI > 1282) and persistent duration in reversing doxorubicin (DOX) resistance in K562/A02 cells. 42 also enhanced the potency of other P-gp associated cytotoxic agents with different structures. In further study, remarkably increased intracellular accumulation of Rh123 and DOX in K562/A02 cells was achieved by compound 42, while CYP3A4 activity had no change by compound 42. These results indicate that compound 42 as a relatively safe modulator of P-gp-mediated MDR has good potential for further development. PMID: 31255991 [PubMed - as supplied by publisher]
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research

Related Links:

Publication date: Available online 14 August 2019Source: Seminars in Cancer BiologyAuthor(s): Dharambir Kashyap, Hardeep Singh Tuli, Mukerrem Betul Yerer, Ajay Sharma, Katrin Sak, Saumya Srivastava, Anjana Pandey, Vivek Kumar Garg, Gautam Sethi, Anupam BishayeeAbstractApplication of natural product-based nanoformulations for the treatment of different human diseases, such as cancer, is an emerging field. The conventional cancer therapeutic modalities, including surgery, chemotherapy, immunotherapy, radiotherapy has limited achievements. A larger number of drawbacks are associated with these therapies, including damage to p...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Publication date: December 2019Source: Materials Science and Engineering: C, Volume 105Author(s): Wenqiang Li, Chenfang Xu, Shuxian Li, Xiuying Chen, Xiaoshan Fan, Zhiguo Hu, Yun-Long Wu, Zibiao LiAbstractAn amphiphilic star-shaped copolymer β-CD-g-PCL-SS-PEG-FA, consisting of a β-cyclodextrin (β-CD) core as well as grafted with bioreducible disulfide linkage in PCL-SS-PEG multiarms and targeting folic acid (FA) as end moiety, is designed with unimolecular micelles formation ability for targeted transport of chemotherapeutics to drug resistant tumor cells. Firstly, β-CD was utilized as core to growth PC...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research
ConclusionsThe TPGS ‐conjugated liposomes showed significant advantagesin vitro compared with the PEG ‐conjugated liposomes. The TPGS‐conjugated liposomes could reverse the MDR and enhance breast cancer therapy.
Source: Journal of Pharmacy and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Research Paper Source Type: research
Conclusion: DOX@pPGNCs present strong potential to overcome MDR in cancer.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
In this study, based on nucleolin’s active transport property to the nucleus and its affinity with aptamer, we developed a nuclear-targeted delivery system to circumvention of drug resistance in breast cancer (MCF-7/Adr). Dox·HCl inserted in the aptamer AS1411 (Ap-Dox) was encapsulated in the aqueous interior of liposome (Lip(Ap-Dox)). In vitro studies showed that after the Lip(Ap-Dox) diffusing into MCF-7/Adr cells, Ap-Dox complex bound with nucleolin strongly and eventually entered the cell nuclei. By using this drug delivery system, Dox·HCl can efficiently accumulated in the nuclei to effectively kill the cancer cells.
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
In this study, based on nucleolin's active transport property to the nucleus and its affinity with aptamer, we developed a nuclear-targeted delivery system to circumvention of drug resistance in breast cancer (MCF-7/Adr). Dox·HCl inserted in the aptamer AS1411 (Ap-Dox) was encapsulated in the aqueous interior of liposome (Lip(Ap-Dox)). In vitro studies showed that after the Lip(Ap-Dox) diffusing into MCF-7/Adr cells, Ap-Dox complex bound with nucleolin strongly and eventually entered the cell nuclei. By using this drug delivery system, Dox·HCl can efficiently accumulated in the nuclei to effectively kill the ...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
Development of high‑resolution melting analysis for ABCB1 promoter methylation: Clinical consequences in breast and ovarian carcinoma. Oncol Rep. 2019 Jun 05;: Authors: Vaclavikova R, Klajic J, Brynychova V, Elsnerova K, Alnaes GIG, Tost J, Kristensen VN, Rob L, Kodet R, Skapa P, Mrhalova M, Soucek P Abstract Multidrug resistance to anticancer drugs, which is often associated with enhanced expression of the ATP‑binding cassette (ABC) transporter P‑glycoprotein (encoded by the ABCB1 gene) may limit the effects of cancer therapy. Epigenetic regulation of ABCB1 expression may thus have a clinical im...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
In this study, a RGD conjugated, pH sensitive lipid was synthesized using glycerin monostearate (GMS) and adipic acid dihydrazide (HZ) as lipid materials and named RGD-HZ-GMS. RGD-HZ-GMS was applied to encapsulate DOX to construct a RGD modified, DOX loaded SLNs (RGD-DOX-SLNs). To evaluate the anticancer effect of RGD-DOX-SLNs, breast cancer cell line (MCF-7 cells) and DOX resistant cell line (MCF-7/ADR cells) were used. in vivo tumor suspension and toxicity effects were evaluated on mice bearing MCF-7/ADR cells breast cancer model. RGD-DOX-SLNs had a uniformly spherical shape. The mean particle size and zeta potential of ...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
In this study, a RGD conjugated, pH sensitive lipid was synthesized using glycerin monostearate (GMS) and adipic acid dihydrazide (HZ) as lipid materials and named RGD-HZ-GMS. RGD-HZ-GMS was applied to encapsulate DOX to construct a RGD modified, DOX loaded SLNs (RGD-DOX-SLNs). To evaluate the anticancer effect of RGD-DOX-SLNs, breast cancer cell line (MCF-7 cells) and DOX resistant cell line (MCF-7/ADR cells) were used. in vivo tumor suspension and toxicity effects were evaluated on mice bearing MCF-7/ADR cells breast cancer model. RGD-DOX-SLNs had a uniformly spherical shape. The mean particle size and zeta potential of ...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
This article is protected by copyright. All rights reserved. PMID: 31136035 [PubMed - as supplied by publisher]
Source: Cell Biology International - Category: Cytology Authors: Tags: Cell Biol Int Source Type: research
More News: Cancer | Cancer & Oncology | Cancer Therapy | Chemistry | Multidrug Resistance | Science | Study