Medicinal Chemistry Research最新文献_第9页

Synthesis of 6-dialkylaminopyrimidine carboxamide analogues and their anti-tubercular properties 6-二烷基氨基嘧啶甲酰胺类似物的合成及其抗结核特性

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-10-18 DOI: 10.1007/s00044-024-03319-8

Ronewa Tshinavhe, Nashied Peton, Sandile B. Simelane, Paseka T. Moshapo

{"title":"Synthesis of 6-dialkylaminopyrimidine carboxamide analogues and their anti-tubercular properties","authors":"Ronewa Tshinavhe, Nashied Peton, Sandile B. Simelane, Paseka T. Moshapo","doi":"10.1007/s00044-024-03319-8","DOIUrl":"10.1007/s00044-024-03319-8","url":null,"abstract":"<div><p>Tuberculosis (TB) continues to be a threat to global health stability. Pyrimidine carboxamides have demonstrated potent anti-tubercular properties against clinical <i>Mycobacterium tuberculosis</i>, the causative agent of TB. Herein, we report a follow-up study on the synthesis of pyrimidine carboxamide molecular analogues and their anti-TB evaluation. In total, a library consisting of 37 new compounds is reported. Seven compounds (<b>7b</b>, <b>7d</b>, <b>7m</b>, <b>7p</b>, <b>7q</b>, <b>7aa</b>, and <b>7ah</b>) demonstrated excellent in vitro activities with MIC<sub>90</sub> values below 1.00 µM. Apart from compound <b>7ah</b>, compounds with improved aqueous solubility properties had lower anti-TB potency. Preliminary mode of action studies using bioluminescence assays indicate that the active compounds do not affect the integrity of mycobacterial DNA or the cell wall. The active compounds were also found to be bactericidal against replicating H37Rv <i>Mtb</i> strain.</p><div><figure><div><div><picture><img></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 12","pages":"2491 - 2516"},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00044-024-03319-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural modifications of berberine and the lipid-regulating effects of its derivatives 小檗碱的结构修饰及其衍生物的调脂作用

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-10-15 DOI: 10.1007/s00044-024-03321-0

Yun Lu, Mengxuan Yin, Yuting Lai, Xinyi Ye, Meiling Chen, Yubo Li

{"title":"Structural modifications of berberine and the lipid-regulating effects of its derivatives","authors":"Yun Lu, Mengxuan Yin, Yuting Lai, Xinyi Ye, Meiling Chen, Yubo Li","doi":"10.1007/s00044-024-03321-0","DOIUrl":"10.1007/s00044-024-03321-0","url":null,"abstract":"<div><p>Hyperlipidemia refers to one or more diseases with unbalanced lipid structure in plasma, which is called dyslipidemia in modern medicine. Natural ingredients are an essential source for developing new medications. Berberine (BBR), the tricyclic triterpene quaternary ammonium molecule, is commonly found in the plant world and exhibits significant biological activity in various therapeutic areas, including cancer, inflammation, metabolic disorders, cardiovascular and allergic diseases, and more. Many BBR derivatives have been created and are being developed to address their drawbacks, such as adverse effects due to poor action due to poor water solubility and limited bioavailability. Recently, researchers have modified the many positions that affect cholesterol-lowering activity because of their distinct mechanisms of action, including C-2,3, C-7, C-8, C-9, C-10, C-11, and C-12. This paper reviews the properties of BBR in lipid-lowering, including structural diversity, structural modifications with lipid-lowering effects, synthesis of BBR derivatives, lipid-lowering properties of its derivatives, and corresponding SAR values. These reviews will help to investigate the lipid-lowering effects of BBR and provide guidance for the development of new lipid-lowering drugs. Ultimately, this review is intended to serve as a foundation for future chemical research and assist in the search for potential cholesterol-lowering therapeutics.</p></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"34 1","pages":"1 - 18"},"PeriodicalIF":2.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quinazoline derivatives and hybrids: recent structures with potent bioactivity 喹唑啉衍生物和混合物：具有强大生物活性的最新结构

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-10-07 DOI: 10.1007/s00044-024-03318-9

Ibrahim A. Bala, Abdullah M. Asiri, Reda M. El-Shishtawy

引用次数: 0

Benzothiazole derivatives as effective α-glucosidase inhibitors: an insight study of structure-activity relationships and molecular targets 苯并噻唑衍生物作为有效的 α-葡萄糖苷酶抑制剂：结构-活性关系和分子靶标的深入研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-09-23 DOI: 10.1007/s00044-024-03314-z

Zebabanu Khalifa, Rachana Upadhyay, Amit B. Patel

{"title":"Benzothiazole derivatives as effective α-glucosidase inhibitors: an insight study of structure-activity relationships and molecular targets","authors":"Zebabanu Khalifa, Rachana Upadhyay, Amit B. Patel","doi":"10.1007/s00044-024-03314-z","DOIUrl":"10.1007/s00044-024-03314-z","url":null,"abstract":"<div><p>In treating the major metabolic disorder diabetes mellitus type-2, the <i>α</i>-glucosidase enzyme inhibitors play an effective role due to their vital capability of polysaccharide hydrolyzation. A well-known <i>α</i>-glucosidase inhibitor drug such as acarbose and miglitol can provide in vivo and in vitro efficacy against diabetes. Subsequently, these clinically approved drugs’ long-term side effects and metabolic resistance can enhance the search for novel small molecule-based α-glucosidase enzyme inhibitors to cure diabetes mellitus. In this present review, benzothiazole-based <i>α</i>-glucosidase inhibitors have been highlighted with their enriched structure-activity relationships containing the published research from (2013–2023), and we also discussed its in silico molecular docking mode of action. Most of the reported benzothiazole-based hybrids exhibited superior potency in vitro compared to approved drugs due to the vast probabilities of the chemical modifications and ligand-protein interactions with the benzothiazole ring. Moreover, significant hydrophobic target interactions, including <i>π</i>-<i>π</i> stacking, <i>π</i>-sulphur, <i>π</i>-cation, and <i>π</i>-anion, were observed during the entire study, which improved the inhibition target potency. The active target residues of <i>α</i>-glucosidase also developed sufficient binding pocket interaction with benzothiazole molecules and reduced the harmful effects. Hence, this study can provide a better understanding of the structural pattern with the in silico-based modification of benzothiazole scaffolds to improve current medication treatments for type-2 diabetes mellitus.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 12","pages":"2347 - 2371"},"PeriodicalIF":2.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of new Michael acceptors with cinnamamide scaffold as potential anti-breast cancer agents: cytotoxicity and ADME in silico studies 以肉桂酰胺为支架合成新的迈克尔受体，作为潜在的抗乳腺癌药物：细胞毒性和 ADME 的硅学研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-09-17 DOI: 10.1007/s00044-024-03307-y

Ruth P. Paulino, Rosemeire B. Alves, Heveline Silva, Rossimiriam P. de Freitas

{"title":"Synthesis of new Michael acceptors with cinnamamide scaffold as potential anti-breast cancer agents: cytotoxicity and ADME in silico studies","authors":"Ruth P. Paulino, Rosemeire B. Alves, Heveline Silva, Rossimiriam P. de Freitas","doi":"10.1007/s00044-024-03307-y","DOIUrl":"https://doi.org/10.1007/s00044-024-03307-y","url":null,"abstract":"<p>In pursuit of potent inhibitors with antiproliferative effects against breast cancer, fifteen new compounds containing a Michael Acceptor Moiety (MAM) were synthesized. The cinnamamide scaffold, a natural source of MAM, was chosen for its versatile structural framework, which offers rich potential for chemical modifications and optimization of biological activity. The first step consisted of obtaining five unprotected amines (<b>5a</b>-<b>e</b>), yielding between 40% and 90% yield. Subsequently, these amines were coupled with various cinnamic acid derivatives, resulting in target products in yields ranging from 30% to 94%. This study aimed to assess the impact of these compounds on cell viability, focusing on two human breast cancer cell lines, MCF-7 and MDA-MB-231. Among the compounds examined, eight (<b>7a</b>, <b>7b</b>, <b>7d</b>, <b>7f</b>-<b>i</b>, <b>7l</b>) showed activity against MDA cells (IC<sub>50</sub> range: 2.5–53.0 µM), and five (<b>7b</b>, <b>7 g</b>-<b>i</b>, <b>7l</b>) showed activity against MCF-7 cells (IC<sub>50</sub> range: 11.2–50.6 µM). <b>7f</b> was the most active molecule, with an IC<sub>50</sub> of 2.5 µM toward MDA cells and a good selective index (SI = 7.9) toward a normal cell line (MCF-10A). In silico ADME studies were carried out with prospective compounds using the SwissADME tool.</p>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"48 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142263863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Iridoid for drug discovery: Structural modifications and bioactivity studies 用于药物发现的类铱：结构修饰和生物活性研究

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-09-16 DOI: 10.1007/s00044-024-03311-2

Mingtao Wang, Xinyue Zheng, Meng Yang, Jiating Ni, Qian Xiao, Hua Han, Peiliang Dong

引用次数: 0

Correction: Substituted furan-carboxamide and Schiff base derivatives as potential hypolipidemic compounds: evaluation in Triton WR-1339 hyperlipidemic rat model 更正：作为潜在降血脂化合物的取代呋喃甲酰胺和希夫碱衍生物：在 Triton WR-1339 高血脂大鼠模型中的评估

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-09-16 DOI: 10.1007/s00044-024-03300-5

Buthaina Hussein, Mohammad Alwahsh, Yusuf Al-Hiari, Laurance Bourghli, Basmah Al-Jammal, Tareq Al-Qirim, Nader R. AlBujuq, Rania Abu-zaid, Fadi G. Saqallah, Lama Hamadneh

引用次数: 0

Synthesis and antiproliferative activity of 7-substituted amide estradiol derivatives 7 取代酰胺类雌二醇衍生物的合成和抗增殖活性

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-09-16 DOI: 10.1007/s00044-024-03301-4

Chun-Fang Gan, Ying Li, Hua-Long Chen, Jia-Wei Yao, Yun-Qiong Gu, Bin Su, Zhi-Wei Zhong, Jian-Guo Cui, Yan-Min Huang, Zhi-Ping Liu

引用次数: 0

Quinazolinone-based subchemotypes for targeting HIV-1 capsid protein: design and synthesis 基于喹唑啉酮的用于靶向 HIV-1 外壳蛋白的亚化学型：设计与合成

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-09-15 DOI: 10.1007/s00044-024-03305-0

Thamina Akther, William M. McFadden, Huanchun Zhang, Karen A. Kirby, Stefan G. Sarafianos, Zhengqiang Wang

引用次数: 0

Medicinal significance of sp2/sp3 hybridized at C-3-substituted indole-containing lead molecules and FDA-approved drugs sp2/sp3杂化在C-3取代的含吲哚先导分子和FDA批准药物的药用意义

IF 2.6 4区医学

Medicinal Chemistry Research Pub Date : 2024-09-13 DOI: 10.1007/s00044-024-03308-x

Mohd Faiyyaz, Akanksha Tiwari, Nuzhat Bashir, Malik Nasibullah, Sahir Sultan Alvi, Mohammed Haris Siddiqui, Mohd Asif

{"title":"Medicinal significance of sp2/sp3 hybridized at C-3-substituted indole-containing lead molecules and FDA-approved drugs","authors":"Mohd Faiyyaz, Akanksha Tiwari, Nuzhat Bashir, Malik Nasibullah, Sahir Sultan Alvi, Mohammed Haris Siddiqui, Mohd Asif","doi":"10.1007/s00044-024-03308-x","DOIUrl":"10.1007/s00044-024-03308-x","url":null,"abstract":"<div><p>Herein, the privilege in favor of biological importance of indole-containing scaffolds related to the semi-synthetic and extracted from natural sources is summarized. Such compounds have shown notable medicinal significance and are used in the treatment of various carcinomas after FDA approval. The chemistry of indoles’ skeleton derivatives showed various conformations at specific conditions, including tautomerization, when they came into contact with polar solvents; consequently, such phenomena are responsible for enhancing the biological effect on enzymes. In the foregoing review study in the past decade, we demonstrated the biological significance and the transformation of drug analysis owing to resonating structures. Functionalize groups, it was noted that <i>pi</i>-bonds-unsaturated functions, <i>sp</i><sup><i>1/2/3</i></sup> hybridized methylene groups, cyclic ethers, primary amino groups, halogens, and staggered conformations displayed the most potent active drug-like molecules. The aim of this report is that drugs like lead molecules could be derivatized for the discovery of more effective drugs on the basis of their possible active sites on the surface in the future.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":699,"journal":{"name":"Medicinal Chemistry Research","volume":"33 12","pages":"2306 - 2328"},"PeriodicalIF":2.6,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0