Drugs and Drug Candidates最新文献

Biological Profile of Synthetic and Natural Indole Derivatives: Paving New Paths in Cancer Treatment 合成和天然吲哚衍生物的生物学特性：为癌症治疗开辟新道路

Drugs and Drug Candidates Pub Date : 2024-07-19 DOI: 10.3390/ddc3030029

Ana Margarida Janeiro, Carolinal S Marques

{"title":"Biological Profile of Synthetic and Natural Indole Derivatives: Paving New Paths in Cancer Treatment","authors":"Ana Margarida Janeiro, Carolinal S Marques","doi":"10.3390/ddc3030029","DOIUrl":"https://doi.org/10.3390/ddc3030029","url":null,"abstract":"The indole scaffold is considered a privileged framework in the design and synthesis of several active pharmaceutical ingredients, particularly as promising anticancer agents. Its presence in several bioactive natural compounds has caught the attention of the scientific community, which has been committed to unveiling its biosynthetic pathways and generating multiple derivatives with innovative synthetic routes. The large variety of structural derivatives enhances their use in multiple bioapplications and pharmacological activities. In this review, the reader will have easy access to some examples of natural and synthetic indole derivatives with antimicrobial, antidepressant, anti-inflammatory, antiviral, antimigraine, and antiemetic activity. However, the main topic of this review is related to cancer and the importance of indole derivatives as promising anticancer drugs. Two of the reasons why cancer is considered a massive problem worldwide are attributed to the struggle to develop target-specific drugs while avoiding drug resistance. Among countless drugs targeting specific proteins involved in tumorigenesis, prompting life quality in the treatment of several cancer types, protein kinases, desoxyribonucleic acid topoisomerases, and P-glycoprotein have been shown to be the main targets when it comes to the development of novel anticancer agents. Furthermore, indole and its derivatives are also studied regarding affinity to other targets related to cancer. This review aims to highlight the utility of the indole scaffold in anticancer drug design, inspiring the creation and synthesis of new derivatives that target specific proteins and address drug resistance challenges.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":" 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141822395","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

Indazole–Quinolone Hybrids as Anti-Virulence Agents against Pseudomonas aeruginosa 吲唑-喹诺酮杂化物作为铜绿假单胞菌的抗真菌剂

Drugs and Drug Candidates Pub Date : 2024-07-19 DOI: 10.3390/ddc3030030

Marie Hanot, Marine Duplantier, C. Dalle, Yani Ren, S. Da Nascimento, Jean-Paul Becker, N. Taudon, Elodie Lohou, P. Sonnet

{"title":"Indazole–Quinolone Hybrids as Anti-Virulence Agents against Pseudomonas aeruginosa","authors":"Marie Hanot, Marine Duplantier, C. Dalle, Yani Ren, S. Da Nascimento, Jean-Paul Becker, N. Taudon, Elodie Lohou, P. Sonnet","doi":"10.3390/ddc3030030","DOIUrl":"https://doi.org/10.3390/ddc3030030","url":null,"abstract":"Antibiotic resistance is a critical public health issue. Among the multi-drug resistant microorganisms in question, Pseudomonas aeruginosa has been designated by the WHO as a priority threat. Its virulence is orchestrated through quorum sensing (QS). This sophisticated communication network relies on the release and perception of autoinducers acting as population density indicators. Therefore, the interest of a quorum silencing pharmacological approach has unfolded to quench bacterial pathogenicity without impairing growth. In this article, we reported the development of a family of indazole–quinolone hybrids as anti-virulence agents. These new biaromatic compounds were designed as potential specific QS quenchers against P. aeruginosa. Our transdisciplinary research methodology included their synthesis using palladocatalyzed cross-coupling reactions, as well as their in silico physicochemical and in vitro biological evaluation. The hit 7-chloro-2-indazolyl-4-quinolone Ie shows a promising anti-biofilm and anti-pyocyanin efficiency (35% inhibition at 25 µM and 35% inhibition at 100 µM, respectively) without an anti-pseudomonal bacteriostatic effect. It also demonstrated a moderate eukaryotic cytotoxicity. Its anti-QS properties have been investigated using metabolomic and molecular modelling studies.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":" 1228","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141823415","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

Essential Oil of Psidium glaziovianum Kiaersk Alleviates the Effects of Complete Freund’s Adjuvant (CFA)-Induced Arthritis by Regulating Inflammation and Oxidative Stress 通过调节炎症和氧化应激减轻完全弗氏佐剂（CFA）诱发的关节炎的影响

Drugs and Drug Candidates Pub Date : 2024-05-07 DOI: 10.3390/ddc3020023

Wêndeo Kennedy Costa, João Victor de Oliveira Alves, Beatriz Meyruze Barros Da Fonseca, V. Silva, Rafael Jardim Ferreira, T. Napoleão, P. Paiva, M. Correia, A. Oliveira, Márcia Vanusa da Silva

{"title":"Essential Oil of Psidium glaziovianum Kiaersk Alleviates the Effects of Complete Freund’s Adjuvant (CFA)-Induced Arthritis by Regulating Inflammation and Oxidative Stress","authors":"Wêndeo Kennedy Costa, João Victor de Oliveira Alves, Beatriz Meyruze Barros Da Fonseca, V. Silva, Rafael Jardim Ferreira, T. Napoleão, P. Paiva, M. Correia, A. Oliveira, Márcia Vanusa da Silva","doi":"10.3390/ddc3020023","DOIUrl":"https://doi.org/10.3390/ddc3020023","url":null,"abstract":"Rheumatoid arthritis (RA) is a chronic and debilitating condition that affects a significant number of individuals worldwide. Unfortunately, the currently available therapeutic approaches often yield unsatisfactory results and may be accompanied by harmful side effects. A medicinal plant called Psidium glaziovianum Kiaersk has potential benefits in the treatment of this condition due to its anti-inflammatory and analgesic properties. In this study, our objective was to investigate the potential therapeutic effects of P. glaziovianum essential oil (PgEO) in alleviating arthritis symptoms in mice induced by Complete Freund’s Adjuvant (CFA). The effect of P. glaziovianum essential oil was evaluated in mice with Complete Freund’s Adjuvant (CFA)-induced arthritis. Edema sizes, macroscopic and radiographic images, cytokine levels, and oxidative stress were evaluated. Administration of PgEO at dosages of 50 and 100 mg/kg effectively prevented CFA-induced osteoarticular changes in arthritic mice, resulting in a significant reduction in joint damage. Additionally, the PgEO treatment exhibited the ability to minimize edema, a common symptom associated with arthritis. Furthermore, PgEO can modulate the levels of pro-inflammatory cytokines and oxidative stress, both of which play crucial roles in the progression of the disease. In conclusion, our study suggests that PgEO holds great potential as a natural therapeutic agent for rheumatoid arthritis.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"29 46","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141004599","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

Preclinical Testing of Chronic ICA-1S Exposure: A Potent Protein Kinase C-ι Inhibitor as a Potential Carcinoma Therapeutic 慢性 ICA-1S 暴露的临床前测试：作为潜在癌症治疗药物的强效蛋白激酶 C-ι 抑制剂

Drugs and Drug Candidates Pub Date : 2024-05-07 DOI: 10.3390/ddc3020022

Christopher A. Apostolatos, W. S. Ratnayake, S. Breedy, Jacqueline Kai Chin Chuah, James Alastair Miller, Daniele Zink, Marie Bourgeois, M. Acevedo-Duncan

{"title":"Preclinical Testing of Chronic ICA-1S Exposure: A Potent Protein Kinase C-ι Inhibitor as a Potential Carcinoma Therapeutic","authors":"Christopher A. Apostolatos, W. S. Ratnayake, S. Breedy, Jacqueline Kai Chin Chuah, James Alastair Miller, Daniele Zink, Marie Bourgeois, M. Acevedo-Duncan","doi":"10.3390/ddc3020022","DOIUrl":"https://doi.org/10.3390/ddc3020022","url":null,"abstract":"Protein kinase C-iota (PKC-ι) is an oncogene overexpressed in many cancer cells including prostate, breast, ovarian, melanoma, and glioma cells. Previous in vitro studies have shown that 5-amino-1-((1R,2S,3R,4R)-2-3-dihydroxy-4-(hydroxymethyl)cyclopentyl)-1H-imidazole-4-carboxamide (ICA-1S), a PKC-ι-specific inhibitor, has low toxicity in both acute and sub-acute mouse model toxicological testing and is an effective therapeutic against several cancer cell lines showing significant reductions in tumor growth when treating athymic nude mice with xenografted carcinoma cell lines. To further assess ICA-1S as a possible therapeutic agent, chronic mouse model toxicological testing was performed in vivo to provide inferences concerning the long-term effects and possible health hazards from repeated exposure over a substantial part of the animal’s lifespan. Subjects survived well after 30, 60, and 90 days of doses ranging from 50 mg/kg to 100 mg/kg. Heart, liver, kidney, and brain tissues were then analyzed for accumulations of ICA-1S including the measured assessment of aspartate transaminase (AST), alkaline phosphatase (ALK-P), gamma-glutamyl transferase (GGT), troponin, and C-reactive protein (CRP) serum levels to assess organ function. Predictive in vitro/in silico methods were used to predict compound-induced direct hepatocyte toxicity or renal proximal tubular cell (PTC) toxicity in humans based on the high-content imaging (HCI) of compound-treated cells in combination with phenotypic profiling. In conclusion, ICA-1S shows low toxicity in both acute and chronic toxicology studies, and shows promise as a potential therapeutic.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"31 32","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141005578","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

Zilucoplan: A Newly Approved Macrocyclic Peptide for Treatment of Anti-Acetylcholine Receptor Positive Myasthenia Gravis Zilucoplan：一种新批准用于治疗抗乙酰胆碱受体阳性肌萎缩症的大环肽

Drugs and Drug Candidates Pub Date : 2024-03-27 DOI: 10.3390/ddc3020018

Lia Costa, C. Fernandes

引用次数: 0

Correction: Marceau, F. Drugs of the Kallikrein–Kinin System: An Overview. Drugs Drug Candidates 2023, 2, 538–553 更正：Marceau, F. Drugs of the Kallikrein-Kinin System：An Overview.Drugs Drug Candidates 2023, 2, 538-553

Drugs and Drug Candidates Pub Date : 2024-02-22 DOI: 10.3390/ddc3010012

François Marceau

引用次数: 0

31st Annual GP2A Medicinal Chemistry Conference 第 31 届 GP2A 药物化学年会

Drugs and Drug Candidates Pub Date : 2024-02-22 DOI: 10.3390/ddc3010013

N. Primas, Caroline Castera-Ducros, Romain Paoli-Lombardo, C. Curti, F. Mathias, P. Rathelot, Pascal Marchand, Patrice Vanelle

引用次数: 0

Isolation and Characterization of Antimicrobial Constituent(s) from the Stem of Cissus populnea Guill. & Perr. 从 Cissus populnea Guill.

Drugs and Drug Candidates Pub Date : 2024-02-19 DOI: 10.3390/ddc3010010

Anita Alex-Asaolu, Ahmad Uba, Umar Abubakar Birnin-Yauri, A. J. Yusuf

{"title":"Isolation and Characterization of Antimicrobial Constituent(s) from the Stem of Cissus populnea Guill. & Perr.","authors":"Anita Alex-Asaolu, Ahmad Uba, Umar Abubakar Birnin-Yauri, A. J. Yusuf","doi":"10.3390/ddc3010010","DOIUrl":"https://doi.org/10.3390/ddc3010010","url":null,"abstract":"Cissus populnea Guill. & Perr. (Vitaceae) is used in traditional medicine to treat microbial infections, venereal diseases and infertility, among others. The aim of this research is to isolate and characterize the antimicrobial constituent(s) from the stem of C. populnea. The n-butanol fraction of C. populnea, being most active, was subjected to silica gel column chromatography, which led to the isolation of white solid and white crystalline substances coded compounds C1 and C4C5, respectively. Spectral analysis (1D and 2D-NMR) of the isolated compounds and comparison with the literature data indicated C1 to be Bis-(2-ethyloctyl)-phthalate and C4C5 to be a mixture of stigmasterol and β-sitosterol; C4C5 exhibited a zone of inhibition ranging from 24 to 29 mm against the test organisms with Candida albicans being the most sensitive organism while Trichophyton rubrum was the least sensitive organism. Of the standard drugs, ciprofloxacin had 27–37 mm while fluconazole and fulcin exhibited zones of inhibition ranging from 34 mm to 29–32 mm, respectively. The MIC and MBC/MFC values for C4C5 ranges from 12.5 to 25.0 µg/cm3 and 25.0 to 50.0 µg/cm3 against methicillin-resistant Staphylococcus aureus, Staphylococcus. aureus, Escherichia coli, Candida albicans, Trichophyton rubrum and Trichophyton mentagrophyte, respectively. In conclusion, Bis-(-(2-ethyloctyl)-phthalate) and a mixture of stigmasterol and β-sitosterol were identified for the first time from the stem of C. populnea.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"220 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140451268","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

Plant-Derived Natural Products: A Source for Drug Discovery and Development 植物提取的天然产品：药物发现和开发的源泉

Drugs and Drug Candidates Pub Date : 2024-02-19 DOI: 10.3390/ddc3010011

N. Chaachouay, L. Zidane

{"title":"Plant-Derived Natural Products: A Source for Drug Discovery and Development","authors":"N. Chaachouay, L. Zidane","doi":"10.3390/ddc3010011","DOIUrl":"https://doi.org/10.3390/ddc3010011","url":null,"abstract":"For thousands of years, nature has been a source of medical substances, and an astounding numeral of contemporary remedies have been identified from natural origins. Plants have long been used as folk herbal medicines to treat various disorders, and their different natural products have inspired the design, discovery, and development of new drugs. With the invention of recent molecular targets based on proteins, there is a growing need for fresh chemical diversification in screening. Natural products will play a vital part in supplying this need via the continuous exploration of global biodiversity, the majority of which remains unexplored. Even though drug discovery from medicinal plants remains an important source of novel therapeutic leads, various hurdles exist, including identifying and executing suitable high-throughput screening bioassays, scaling up the supply of bioactive molecules, and acquiring plant materials. Investigating these natural resources takes multi-disciplinary, nationwide, and global partnerships in design, synthesis, discovery, and drug development techniques. This review article discusses current advancements and future approaches for discovering natural items such as health- and wellness-promoting remedies. It also summarizes strategies to unify the therapeutic use of plant-derived natural products worldwide to support future drug discoveries derived from plant sources.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"32 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140449569","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

Revolutionizing Drug Discovery: A Comprehensive Review of AI Applications 革新药物发现：人工智能应用综述

Drugs and Drug Candidates Pub Date : 2024-02-13 DOI: 10.3390/ddc3010009

Rushikesh Dhudum, Ankit Ganeshpurkar, Atmaram Pawar

{"title":"Revolutionizing Drug Discovery: A Comprehensive Review of AI Applications","authors":"Rushikesh Dhudum, Ankit Ganeshpurkar, Atmaram Pawar","doi":"10.3390/ddc3010009","DOIUrl":"https://doi.org/10.3390/ddc3010009","url":null,"abstract":"The drug discovery and development process is very lengthy, highly expensive, and extremely complex in nature. Considering the time and cost constraints associated with conventional drug discovery, new methods must be found to enhance the declining efficiency of traditional approaches. Artificial intelligence (AI) has emerged as a powerful tool that harnesses anthropomorphic knowledge and provides expedited solutions to complex challenges. Advancements in AI and machine learning (ML) techniques have revolutionized their applications to drug discovery and development. This review illuminates the profound influence of AI on diverse aspects of drug discovery, encompassing drug-target identification, molecular properties, compound analysis, drug development, quality assurance, and drug toxicity assessment. ML algorithms play an important role in testing systems and can predict important aspects such as the pharmacokinetics and toxicity of drug candidates. This review not only strengthens the theoretical foundation and development of this technology, but also explores the myriad challenges and promising prospects of AI in drug discovery and development. The combination of AI and drug discovery offers a promising strategy to overcome the challenges and complexities of the pharmaceutical industry.","PeriodicalId":131152,"journal":{"name":"Drugs and Drug Candidates","volume":"16 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139779711","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