Tapping into the antitubercular potential of 2,5-dimethylpyrroles: A structure-activity relationship interrogation
Eur J Med Chem. 2022 Apr 21;237:114404. doi: 10.1016/j.ejmech.2022.114404. Online ahead of print.ABSTRACTAn exploration of the chemical space around a 2,5-dimethylpyrrole scaffold of antitubercular hit compound 1 has led to the identification of new derivatives active against Mycobacterium tuberculosis and multidrug-resistant clinical isolates. Analogues incorporating a cyclohexanemethyl group on the methyleneamine side chain at C3 of the pyrrole core, including 5n and 5q, exhibited potent inhibitory effects against the M. tuberculosis strains, substantiating the essentiality of the moiety to their antimycobacterial activi...
Source: European Journal of Medicinal Chemistry - April 29, 2022 Category: Chemistry Authors: Dorothy Semenya Meir Touitou Domiziana Masci Camila Maringolo Ribeiro Fernando Rogerio Pavan Guilherme Felipe Dos Santos Fernandes Beatrice Gianibbi Fabrizio Manetti Daniele Castagnolo Source Type: research

Identification of novel and potent PROTACs targeting FAK for non-small cell lung cancer: Design, synthesis, and biological study
Eur J Med Chem. 2022 Apr 23;237:114373. doi: 10.1016/j.ejmech.2022.114373. Online ahead of print.ABSTRACTThe intracellular non-receptor tyrosine protein kinase Focal adhesion kinase (FAK) is a key signalling regulator, which mediates tumor survival, invasion, metastasis, and angiogenesis through its kinase catalytic functions and non-kinase scaffolding functions. Previous efforts have clarified that it is crucial to address both FAK kinase and scaffolding functions instead of just inhibiting FAK kinase activity because it may be insufficient to completely block FAK signaling. Proteolysis targeting chimera (PROTAC) technolo...
Source: European Journal of Medicinal Chemistry - April 29, 2022 Category: Chemistry Authors: Yin Sun Ruifeng Wang Yu Sun Lin Wang Yanli Xue Jingkai Wang Tianxiao Wu Wenbo Yin Qiaohua Qin Yixiang Sun Dongmei Zhao Maosheng Cheng Source Type: research

Conformational adjustment overcomes multiple drug-resistance mutants of tropomyosin receptor kinase
Eur J Med Chem. 2022 Apr 25;237:114406. doi: 10.1016/j.ejmech.2022.114406. Online ahead of print.ABSTRACTMutation-induced resistance to targeted drug treatment poses a serious threat to successful chemotherapy. Multiple mutations underlying drug resistance remain a largely unsolved scientific issue. Tropomyosin receptor kinases (TRKs) are promising therapeutic targets for several malignant human cancers, but they have become less effective due to multiple resistance mutations. Thus, TRKs are representative cases to explore the problem of multiple resistance mutations. Here, we proposed a conformational adjustment strategy ...
Source: European Journal of Medicinal Chemistry - April 29, 2022 Category: Chemistry Authors: Long-Can Mei Lin-Sheng Zhuo Hong-Chuang Xu Wei Huang Ge-Fei Hao Guang-Fu Yang Source Type: research

Tapping into the antitubercular potential of 2,5-dimethylpyrroles: A structure-activity relationship interrogation
Eur J Med Chem. 2022 Apr 21;237:114404. doi: 10.1016/j.ejmech.2022.114404. Online ahead of print.ABSTRACTAn exploration of the chemical space around a 2,5-dimethylpyrrole scaffold of antitubercular hit compound 1 has led to the identification of new derivatives active against Mycobacterium tuberculosis and multidrug-resistant clinical isolates. Analogues incorporating a cyclohexanemethyl group on the methyleneamine side chain at C3 of the pyrrole core, including 5n and 5q, exhibited potent inhibitory effects against the M. tuberculosis strains, substantiating the essentiality of the moiety to their antimycobacterial activi...
Source: European Journal of Medicinal Chemistry - April 29, 2022 Category: Chemistry Authors: Dorothy Semenya Meir Touitou Domiziana Masci Camila Maringolo Ribeiro Fernando Rogerio Pavan Guilherme Felipe Dos Santos Fernandes Beatrice Gianibbi Fabrizio Manetti Daniele Castagnolo Source Type: research

Identification of novel and potent PROTACs targeting FAK for non-small cell lung cancer: Design, synthesis, and biological study
Eur J Med Chem. 2022 Apr 23;237:114373. doi: 10.1016/j.ejmech.2022.114373. Online ahead of print.ABSTRACTThe intracellular non-receptor tyrosine protein kinase Focal adhesion kinase (FAK) is a key signalling regulator, which mediates tumor survival, invasion, metastasis, and angiogenesis through its kinase catalytic functions and non-kinase scaffolding functions. Previous efforts have clarified that it is crucial to address both FAK kinase and scaffolding functions instead of just inhibiting FAK kinase activity because it may be insufficient to completely block FAK signaling. Proteolysis targeting chimera (PROTAC) technolo...
Source: European Journal of Medicinal Chemistry - April 29, 2022 Category: Chemistry Authors: Yin Sun Ruifeng Wang Yu Sun Lin Wang Yanli Xue Jingkai Wang Tianxiao Wu Wenbo Yin Qiaohua Qin Yixiang Sun Dongmei Zhao Maosheng Cheng Source Type: research

Conformational adjustment overcomes multiple drug-resistance mutants of tropomyosin receptor kinase
Eur J Med Chem. 2022 Apr 25;237:114406. doi: 10.1016/j.ejmech.2022.114406. Online ahead of print.ABSTRACTMutation-induced resistance to targeted drug treatment poses a serious threat to successful chemotherapy. Multiple mutations underlying drug resistance remain a largely unsolved scientific issue. Tropomyosin receptor kinases (TRKs) are promising therapeutic targets for several malignant human cancers, but they have become less effective due to multiple resistance mutations. Thus, TRKs are representative cases to explore the problem of multiple resistance mutations. Here, we proposed a conformational adjustment strategy ...
Source: European Journal of Medicinal Chemistry - April 29, 2022 Category: Chemistry Authors: Long-Can Mei Lin-Sheng Zhuo Hong-Chuang Xu Wei Huang Ge-Fei Hao Guang-Fu Yang Source Type: research

Discovery a series of quinazolin derivatives as potent AXL inhibitors
Eur J Med Chem. 2022 Apr 6;237:114316. doi: 10.1016/j.ejmech.2022.114316. Online ahead of print.NO ABSTRACTPMID:35483321 | DOI:10.1016/j.ejmech.2022.114316 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - April 28, 2022 Category: Chemistry Authors: Lin-Lin Zhang Jian Wu Dong-Dong Li Xiao-Jun Ji Chang-You Ma Dan Xu Source Type: research

Targeting breast cancer resistance protein (BCRP/ABCG2): Functional inhibitors and expression modulators
Eur J Med Chem. 2022 Apr 6;237:114346. doi: 10.1016/j.ejmech.2022.114346. Online ahead of print.ABSTRACTThe primary source of failure of cancer therapies is multidrug resistance (MDR), which can be caused by different mechanisms, including the overexpression of ABC transporters in cancer cells. Among the 48 human ABC proteins, the breast cancer resistance protein (BCRP/ABCG2) has been described as a pivotal player in cancer resistance. The use of functional inhibitors and expression modulators is a promising strategy to overcome the MDR caused by ABCG2. Despite the lack of clinical trials using ABCG2 inhibitors, many compo...
Source: European Journal of Medicinal Chemistry - April 28, 2022 Category: Chemistry Authors: Ingrid Fatima Zattoni Let ícia Carani Delabio Julia de Paula Dutra Diogo Henrique Kita Gustavo Scheiffer Marina Hembecker Giovana da Silva Pereira Vivian Rotuno Moure Glaucio Valdameri Source Type: research

Discovery of novel non-steroidal selective glucocorticoid receptor modulators by structure- and IGN-based virtual screening, structural optimization, and biological evaluation
This study reported a group of non-steroidal new-scaffold SGRMs, providing valuable clues for the development of novel anti-inflammatory drugs.PMID:35483323 | DOI:10.1016/j.ejmech.2022.114382 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - April 28, 2022 Category: Chemistry Authors: Xueping Hu Jinping Pang Changwei Chen Dejun Jiang Chao Shen Xin Chai Liu Yang Xujun Zhang Lei Xu Sunliang Cui Tingjun Hou Dan Li Source Type: research

Discovery a series of quinazolin derivatives as potent AXL inhibitors
Eur J Med Chem. 2022 Apr 6;237:114316. doi: 10.1016/j.ejmech.2022.114316. Online ahead of print.NO ABSTRACTPMID:35483321 | DOI:10.1016/j.ejmech.2022.114316 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - April 28, 2022 Category: Chemistry Authors: Lin-Lin Zhang Jian Wu Dong-Dong Li Xiao-Jun Ji Chang-You Ma Dan Xu Source Type: research

Targeting breast cancer resistance protein (BCRP/ABCG2): Functional inhibitors and expression modulators
Eur J Med Chem. 2022 Apr 6;237:114346. doi: 10.1016/j.ejmech.2022.114346. Online ahead of print.ABSTRACTThe primary source of failure of cancer therapies is multidrug resistance (MDR), which can be caused by different mechanisms, including the overexpression of ABC transporters in cancer cells. Among the 48 human ABC proteins, the breast cancer resistance protein (BCRP/ABCG2) has been described as a pivotal player in cancer resistance. The use of functional inhibitors and expression modulators is a promising strategy to overcome the MDR caused by ABCG2. Despite the lack of clinical trials using ABCG2 inhibitors, many compo...
Source: European Journal of Medicinal Chemistry - April 28, 2022 Category: Chemistry Authors: Ingrid Fatima Zattoni Let ícia Carani Delabio Julia de Paula Dutra Diogo Henrique Kita Gustavo Scheiffer Marina Hembecker Giovana da Silva Pereira Vivian Rotuno Moure Glaucio Valdameri Source Type: research

Discovery of novel non-steroidal selective glucocorticoid receptor modulators by structure- and IGN-based virtual screening, structural optimization, and biological evaluation
This study reported a group of non-steroidal new-scaffold SGRMs, providing valuable clues for the development of novel anti-inflammatory drugs.PMID:35483323 | DOI:10.1016/j.ejmech.2022.114382 (Source: European Journal of Medicinal Chemistry)
Source: European Journal of Medicinal Chemistry - April 28, 2022 Category: Chemistry Authors: Xueping Hu Jinping Pang Changwei Chen Dejun Jiang Chao Shen Xin Chai Liu Yang Xujun Zhang Lei Xu Sunliang Cui Tingjun Hou Dan Li Source Type: research

Design, synthesis, and evaluation of a novel series of mono-indolylbenzoquinones derivatives for the potential treatment of breast cancer
Eur J Med Chem. 2022 Apr 16;237:114375. doi: 10.1016/j.ejmech.2022.114375. Online ahead of print.ABSTRACTBreast cancer is one of the most common cancers in the world, and pro-apototic drugs activating the apoptotic pathway are a strategy for anticancer therapy. To explore new antineoplastic agents, a series of novel mono-indolylbenzoquinone derivatives have been designed and synthesized. Compared with the lead bis-indolylbenzoquinones, most of the novel mono-indolylbenzoquinone derivatives have significantly increased their activity against A549, HeLa, and especially, MDA-MB-231 cell lines. Among them, 10d has the lowest I...
Source: European Journal of Medicinal Chemistry - April 27, 2022 Category: Chemistry Authors: Jingjing Jia Honglu Yin Chen Chen Mingli Hu Qiu Zhong Shilong Zheng Wei Zhang Haibo Li Liang Xu Guangdi Wang Ling He Source Type: research

Discovery of novel pleuromutilin derivatives as potent antibacterial agents
Eur J Med Chem. 2022 Apr 20;237:114403. doi: 10.1016/j.ejmech.2022.114403. Online ahead of print.ABSTRACTNovel pleuromutilin derivatives with 3,4-dihydropyrimidin and pyrimidine moieties were designed, synthesized, and evaluated for their antibacterial activities. Most of the synthesized derivatives, especially the compounds bearing the pyrimidine moieties, exhibited potent antibacterial activities against methicillin-resistant Staphylococcus aureus BNCC 337371 (MRSA-337371), Staphylococcus aureus ATCC 25923 (S. aureus-25923) and methicillin-resistant Staphylococcus epidermidis ATCC 51625 (MRSE-51625). Compounds 5a, 5g and...
Source: European Journal of Medicinal Chemistry - April 26, 2022 Category: Chemistry Authors: Yuhang Zhou Yunpeng Yi Jiangkun Wang Zheng Yang Qinqin Liu Wanxia Pu Ruofeng Shang Source Type: research

Application of partially aromatic ortho-quionone-methides for the synthesis of novel naphthoxazines with improved antibacterial activity
Eur J Med Chem. 2022 Apr 18;237:114391. doi: 10.1016/j.ejmech.2022.114391. Online ahead of print.ABSTRACTStarting from naphthols and morpholine and using ethyl glyoxylate as the aldehyde component in the modified Mannich reaction, new aminonaphthol derivatives substituted with 2- and 1-naphthol were synthesised. The stabilization of precursor bifunctional compounds via partially aromatic ortho-quinone methide intermediate was tested with different cyclic imines in [4 + 2] cycloaddition. Based on 1H NMR analysis, in the case of new α-amino acid esters the formation of a single product has been assumed. The NOE spectrum pro...
Source: European Journal of Medicinal Chemistry - April 26, 2022 Category: Chemistry Authors: D óra Hegedűs Nikoletta Szemer édi Gabriella Spengler Istv án Szatmári Source Type: research