Drugs and Drug Candidates最新文献_第7页

Angiogenesis under Opioids Preconditioning in Renal Ischemia Reperfusion 阿片预处理对肾缺血再灌注血管生成的影响

Drugs and Drug Candidates Pub Date : 2023-01-07 DOI: 10.3390/ddc2010001

Maritza G. Verdugo-Molinares, A. Franco-Acevedo, Cesar-Ivan Ortiz, José L. Cerino-Recinos, B. Moreno-Carranza, Zesergio Melo

引用次数: 0

Synthesis, Characterization, and Activity of Hydroxymethylnitrofurazone Nanocrystals against Trypanosoma cruzi and Leishmania spp. 羟甲基硝基呋喃酮纳米晶体的合成、表征及抗克氏锥虫和利什曼原虫活性研究。

Drugs and Drug Candidates Pub Date : 2022-12-13 DOI: 10.3390/ddc1010005

C. B. Scarim, Aline de Souza, Débora Soares Souza Marins, E. G. Santos, Lívia de Figueiredo Diniz Castro, I. Caldas, P. F. Espuri, M. Marques, E. Ferreira, N. Bou-Chacra, C. Chin

{"title":"Synthesis, Characterization, and Activity of Hydroxymethylnitrofurazone Nanocrystals against Trypanosoma cruzi and Leishmania spp.","authors":"C. B. Scarim, Aline de Souza, Débora Soares Souza Marins, E. G. Santos, Lívia de Figueiredo Diniz Castro, I. Caldas, P. F. Espuri, M. Marques, E. Ferreira, N. Bou-Chacra, C. Chin","doi":"10.3390/ddc1010005","DOIUrl":"https://doi.org/10.3390/ddc1010005","url":null,"abstract":"Hydroxymethylnitrofurazone (NFOH) is a prodrug of nitrofurazone devoid of mutagenic toxicity, with in vitro and in vivo activity against Trypanosoma cruzi (T. cruzi) and in vitro activity against Leishmania. In this study, we aimed to increase the solubility of NFOH to improve its efficacy against T. cruzi (Chagas disease) and Leishmania species (Leishmaniasis) highly. Two formulations of NFOH nanocrystals (NFOH-F1 and NFOH-F2) were prepared and characterized by determining their particle sizes, size distribution, morphologies, crystal properties, and anti-trypanosomatid activities. Furthermore, cytotoxicity assays were performed. The results showed that the optimized particle size of 108.2 ± 0.8 nm (NFOH-F1) and 132.4 ± 2.3 nm (NFOH-F2) increased the saturation solubility and dissolution rate of the nanocrystals. These formulations exhibited moderate anti-Leishmania effects (Leishmania amazonensis) in vitro and potent in vitro activity against T. cruzi parasites (Y strain). Moreover, both formulations could reduce parasitemia (around 89–95% during the parasitemic peak) in a short animal model trial (Y strain from T. cruzi). These results suggested that the increased water solubility of the NFOH nanocrystals improved their activity against Chagas disease in both in vitro and in vivo assays.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128501049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Xanthene Derivatives Targeting Bacterial Efflux Pumps, Quorum-Sensing, and Biofilm Formation 针对细菌外排泵、群体感应和生物膜形成的杂蒽衍生物

Drugs and Drug Candidates Pub Date : 2022-12-06 DOI: 10.3390/ddc1010004

M. Maia, Fernando Durães, D. Resende, Nikoletta Szemerédi, L. Gales, Paulo Martins-da-Costa, M. Pinto, G. Spengler, E. Sousa

{"title":"Xanthene Derivatives Targeting Bacterial Efflux Pumps, Quorum-Sensing, and Biofilm Formation","authors":"M. Maia, Fernando Durães, D. Resende, Nikoletta Szemerédi, L. Gales, Paulo Martins-da-Costa, M. Pinto, G. Spengler, E. Sousa","doi":"10.3390/ddc1010004","DOIUrl":"https://doi.org/10.3390/ddc1010004","url":null,"abstract":"The rise of multidrug resistance (MDR) bacteria in nosocomial and health-care institutions is widespread and is currently recognized as a major medical challenge. Mechanisms of bacterial resistance, namely, quorum sensing (QS), biofilm formation, and efflux pumps, have been identified as critical biological processes in MDR bacteria. Following previous reports on the activity of phenothiazines against mechanisms of bacterial resistance, in this work we focus on the synthesis of xanthene derivatives aiming to discover phenothiazine bioisosteres with improved activity. Four compounds were obtained from the conjugation of xanthydrol with sulfonamides and aniline and were fully characterized. Their antibacterial activity was assessed considering their minimum inhibitory concentration (MIC) against Gram-positive and Gram-negative strains, efflux pump inhibition, influence on biofilm formation and quorum-sensing (QS) inhibition. It was observed that the MIC of all the tested compounds was above 64 µg/mL The four 9-xanthenyl derivatives obtained, particularly the xanthene sulfonamide derivatives 3b and 3c, showed promising results on QS inhibition with a reduction of pigment production of 48 and 41 mm, and on biofilm formation with a reduction of 78 and 79%, respectively.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130146174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Failed Repurposing of Lysosomotropic Drugs for COVID-19 Treatment or Prevention 在COVID-19治疗或预防中重新使用溶酶体药物失败

Drugs and Drug Candidates Pub Date : 2022-12-02 DOI: 10.3390/ddc1010003

F. Marceau

引用次数: 0

Synthesis, Selective Cytotoxic Activity against Human Breast Cancer MCF7 Cell Line and Molecular Docking of Some Chalcone-Dihydropyrimidone Hybrids 一些查尔酮-二氢嘧啶杂合体的合成、对人乳腺癌MCF7细胞系的选择性细胞毒活性及分子对接

Drugs and Drug Candidates Pub Date : 2022-12-01 DOI: 10.3390/ddc1010002

Eduardo B. Mass, C. A. de Lima, M. G. D’Oca, J. Sciani, G. Longato, D. Russowsky

{"title":"Synthesis, Selective Cytotoxic Activity against Human Breast Cancer MCF7 Cell Line and Molecular Docking of Some Chalcone-Dihydropyrimidone Hybrids","authors":"Eduardo B. Mass, C. A. de Lima, M. G. D’Oca, J. Sciani, G. Longato, D. Russowsky","doi":"10.3390/ddc1010002","DOIUrl":"https://doi.org/10.3390/ddc1010002","url":null,"abstract":"Designed Chalcone-Dihydropyrimidinone hybrid compounds were synthesized expeditiously. The hybridization was performed through the Copper-catalyzed Alkyne-Azide Cycloaddition (CuAAC) from the propargyloxy chalcones and azido-dihydropyrimidinones. The hybrid products were prepared in five steps with a 30–48% overall yield. Most of the compounds showed selective cytotoxicity and lower IC50 values (<10 µM) against MCF-7 (breast adenocarcinoma) cancer. Cytotoxicity was also observed against OVCAR-3 (ovary, adenocarcinoma), NCI/ADR-RES (ovary, multidrug-resistant adenocarcinoma), and U-251 (brain, glioblastoma) cell lines. The potency of the most active hybrids 9d, 9g, and 9h was greater than the individual parental compounds, suggesting the effectiveness of molecular hybridization on the cytotoxicity. Compounds 9d, 9g, and especially 9h showed high selectivity for breast cancer cells (MCF-7) regarding human keratinocytes (HaCaT). Molecular docking calculations for the 9d, 9g, and 9h hybrids in the active site of estrogen supported the hypothesis that the compounds act as ER-α antagonists, disrupting the cell proliferation process of MCF-7, corroborating the potency and selectivity observed for this tumoral cell line.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133082150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Drugs and Drug Candidates: A Challenging Project 药物和候选药物:一个具有挑战性的项目

Drugs and Drug Candidates Pub Date : 2022-07-19 DOI: 10.3390/ddc1010001

J. Vanden Eynde

引用次数: 0