Dimeric peptoids as antibacterial agents
Bioorg Chem. 2024 Apr 3;147:107334. doi: 10.1016/j.bioorg.2024.107334. Online ahead of print.ABSTRACTBuilding upon our previous study on peptoid-based antibacterials which showed good activity against Gram-positive bacteria only, herein we report the synthesis of 34 dimeric peptoid compounds and the investigation of their activity against Gram-positive and Gram-negative pathogens. The newly designed peptoids feature a di-hydrophobic moiety incorporating phenyl, bromo-phenyl, and naphthyl groups, combined with variable lengths of cationic units such as amino and guanidine groups. The study also underscores the pivotal inter...
Source: Bioorganic Chemistry - April 7, 2024 Category: Chemistry Authors: Ghayah Bahatheg Rajesh Kuppusamy Muhammad Yasir Samara Bridge Shyam K Mishra Charles G Cranfield David StC Black Mark Willcox Naresh Kumar Source Type: research
Discovery and development of novel 10,12-disubstituted aloperine derivatives against HCoV-OC43 by targeting allosteric site of host TMPRSS2
Bioorg Chem. 2024 Mar 27;147:107317. doi: 10.1016/j.bioorg.2024.107317. Online ahead of print.ABSTRACTBy inducing steric activation of the 10CH bond with a 12-acyl group to form a key imine oxime intermediate, 20 novel (10S)-10,12-disubstituted aloperine derivatives were successfully synthesized and assessed for their antiviral efficacy against HCoV-OC43. Of them, compound 3i exhibited the moderate activities against HCoV-OC43, as well as against the SARS-CoV-2 variant EG.5.1 with the comparable EC50 values of 4.7 and 4.1 μM. A mechanism study revealed that it inhibited the protease activity of host TMPRSS2 by binding to ...
Source: Bioorganic Chemistry - April 7, 2024 Category: Chemistry Authors: Runze Meng Xiuli Zhong Yue Gong Yulong Shi Jiayu Li Zhiyun Wu Qionglu Duan Xintong Zhang Yuheng Mei Jingyang Zhu Zonggen Peng Yinghong Li Danqing Song Source Type: research
Antimicrobial macrozones interact with biological macromolecules via two-site binding mode of action: Fluorimetric, NMR and docking studies
Bioorg Chem. 2024 Apr 5;147:107338. doi: 10.1016/j.bioorg.2024.107338. Online ahead of print.ABSTRACTMacrozones are novel conjugates of azithromycin and thiosemicarbazones, which exhibit very good in vitro antibacterial activities against susceptible and some resistant bacterial strains thus showing a potential for further development. A combination of spectrometric (fluorimetry, STD and WaterLOGSY NMR) and molecular docking studies provided insights into atomic details of interactions between selected macrozones and biological receptors such as E. coli ribosome and bovine serum albumin. Fluorimetric measurements revealed ...
Source: Bioorganic Chemistry - April 7, 2024 Category: Chemistry Authors: Tomislav Jedna čak Ivana Mikulandra Kristina Smokrovi ć Andrea Hlou šek-Kasun Monika Kapusti ć Kristina Dela š Ivo Piantanida Marta Jurkovi ć Branimir Berto ša Klaus Zangger Predrag Novak Source Type: research
PI3K δ and mTOR dual inhibitors: Design, synthesis and anticancer evaluation of 3-substituted aminomethylquinoline analogues
Bioorg Chem. 2024 Mar 30;147:107323. doi: 10.1016/j.bioorg.2024.107323. Online ahead of print.ABSTRACTPhosphatidylinositide-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) have recently been identified as potential cancer targets. In our work, a new family of quinoline analogues was designed, developed, and evaluated as dual inhibitors of PI3Kδ/mTOR. The preliminary biological activity analysis led to the discovery of the lead compounds 5h and 5e. Compounds 5h and 5e exhibited excellent anti-tumor potency with IC50 of 0.26 µM and 0.34 µM against Ramos cells, respectively. Importantly, based on the enzymatic...
Source: Bioorganic Chemistry - April 7, 2024 Category: Chemistry Authors: Digambar Yevale Nishith Teraiya Twinkle Lalwani Mayur Dalasaniya Khushal Kapadiya Rakesh Kumar Ameta Chetan B Sangani Yong-Tao Duan Source Type: research
Advances in the discovery of activin receptor-like kinase 5 (ALK5) inhibitors
Bioorg Chem. 2024 Apr 3;147:107332. doi: 10.1016/j.bioorg.2024.107332. Online ahead of print.ABSTRACTActivin receptor‑like kinase-5 (ALK5) is an outstanding member of the transforming growth factor-β (TGF-β) family. (TGF-β) signaling pathway integrates pleiotropic proteins that regulate various cellular processes such as growth, proliferation, and differentiation. Dysregulation within the signaling pathway can cause variety of diseases, such as fibrosis, cardiovascular disease, and especially cancer, rendering ALK5 a potential drug target. Hence, various small molecules have been designed and synthesized as potent ALK...
Source: Bioorganic Chemistry - April 6, 2024 Category: Chemistry Authors: Mai A Mansour Ghaneya S Hassan Rabah A T Serya Maiy Y Jaballah Khaled A M Abouzid Source Type: research
Bioisosteric replacement strategy leads to novel DNA gyrase B inhibitors with improved potencies and properties
In this study, a series of N-heteroaryl-substituted 4-hydroxy-2-quinolone-3-carboxamides were developed using the bioisosteric replacement strategy. As a result of our research, we discovered the two most potent GyrB inhibitors (WBX7 and WBX18), with IC50 values of 0.816 µM and 0.137 µM, respectively. Additional antibacterial activity screening indicated that WBX18 possesses the best antibacterial activity against MRSA, VISA, and VRE strains, with MIC values rangingbetween0.5and 2 µg/mL, which was 2 to over 32 times more potent than that of vancomycin. In vitro safety and metabolic stability, as well as in vivo pharmaco...
Source: Bioorganic Chemistry - April 6, 2024 Category: Chemistry Authors: Wenjie Xue Xueping Zuo Xueqi Zhao Xiaomin Wang Xiangyu Zhang Jie Xia Maosheng Cheng Huali Yang Source Type: research
Advances in the discovery of activin receptor-like kinase 5 (ALK5) inhibitors
Bioorg Chem. 2024 Apr 3;147:107332. doi: 10.1016/j.bioorg.2024.107332. Online ahead of print.ABSTRACTActivin receptor‑like kinase-5 (ALK5) is an outstanding member of the transforming growth factor-β (TGF-β) family. (TGF-β) signaling pathway integrates pleiotropic proteins that regulate various cellular processes such as growth, proliferation, and differentiation. Dysregulation within the signaling pathway can cause variety of diseases, such as fibrosis, cardiovascular disease, and especially cancer, rendering ALK5 a potential drug target. Hence, various small molecules have been designed and synthesized as potent ALK...
Source: Bioorganic Chemistry - April 6, 2024 Category: Chemistry Authors: Mai A Mansour Ghaneya S Hassan Rabah A T Serya Maiy Y Jaballah Khaled A M Abouzid Source Type: research
Bioisosteric replacement strategy leads to novel DNA gyrase B inhibitors with improved potencies and properties
In this study, a series of N-heteroaryl-substituted 4-hydroxy-2-quinolone-3-carboxamides were developed using the bioisosteric replacement strategy. As a result of our research, we discovered the two most potent GyrB inhibitors (WBX7 and WBX18), with IC50 values of 0.816 µM and 0.137 µM, respectively. Additional antibacterial activity screening indicated that WBX18 possesses the best antibacterial activity against MRSA, VISA, and VRE strains, with MIC values rangingbetween0.5and 2 µg/mL, which was 2 to over 32 times more potent than that of vancomycin. In vitro safety and metabolic stability, as well as in vivo pharmaco...
Source: Bioorganic Chemistry - April 6, 2024 Category: Chemistry Authors: Wenjie Xue Xueping Zuo Xueqi Zhao Xiaomin Wang Xiangyu Zhang Jie Xia Maosheng Cheng Huali Yang Source Type: research
Discovery of a novel class of rosmarinic acid derivatives as antibacterial agents: Synthesis, structure-activity relationship and mechanism of action
Bioorg Chem. 2024 Mar 28;146:107318. doi: 10.1016/j.bioorg.2024.107318. Online ahead of print.ABSTRACTTwenty-seven rosmarinic acid derivatives were synthesized, among which compound RA-N8 exhibited the most potent antibacterial ability. The minimum inhibition concentration of RA-N8 against both S. aureus (ATCC 29213) and MRSA (ATCC BAA41 and ATCC 43300) was found to be 6 μg/mL, and RA-N8 killed E. coli (ATCC 25922) at 3 μg/mL in the presence of polymyxin B nonapeptide (PMBN) which increased the permeability of E. coli. RA-N8 exhibited a weak hemolytic effect at the minimum inhibitory concentration. SYTOX Green assay, SEM...
Source: Bioorganic Chemistry - April 5, 2024 Category: Chemistry Authors: Yong Wang Zhiguang Liang Yihui Cao Cheung-Hin Hung Ruolan Du Alan Siu-Lun Leung Pui-Kin So Pak-Ho Chan Wing-Leung Wong Yun-Chung Leung Kwok-Yin Wong Source Type: research
Ferroptosis inducers: A new frontier in cancer therapy
Bioorg Chem. 2024 Apr 2;146:107331. doi: 10.1016/j.bioorg.2024.107331. Online ahead of print.ABSTRACTFerroptosis represents a non-apoptotic form of programmed cell death characterized by iron-dependent lipid peroxidation. This cell death modality not only facilitates the direct elimination of cancer cells, but also enhances their susceptibility to other pharmacological anti-cancer agents. The burgeoning interest in ferroptosis has been driven by a growing body of evidence that underscores the efficiency and minimal toxicity of ferroptosis inducers. Traditional inducers, such as erastin and RSL3 have shown substantial promi...
Source: Bioorganic Chemistry - April 5, 2024 Category: Chemistry Authors: Wenjing Ma Naiyuan Hu Wenqian Xu Linxi Zhao Chutong Tian Ken-Ichiro Kamei Source Type: research
Identification of benzo[b]thiophene-1,1-dioxide derivatives as novel PHGDH covalent inhibitors
Bioorg Chem. 2024 Apr 3;146:107330. doi: 10.1016/j.bioorg.2024.107330. Online ahead of print.ABSTRACTThe increased de novo serine biosynthesis confers many advantages for tumorigenesis and metastasis. Phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine biogenesis, exhibits hyperactivity across multiple tumors and emerges as a promising target for cancer treatment. Through screening our in-house compound library, we identified compound Stattic as a potent PHGDH inhibitor (IC50 = 1.98 ± 0.66 µM). Subsequent exploration in structural activity relationships led to the discovery of compound B12 that demon...
Source: Bioorganic Chemistry - April 5, 2024 Category: Chemistry Authors: Xin-Yu Cao Xinge Li Feng Wang Yichen Duan Xingmei Wu Guo-Qiang Lin Meiyu Geng Min Huang Ping Tian Shuai Tang Dingding Gao Source Type: research
Discovery of a novel small-molecule activator of SIRT3 that inhibits cell proliferation and migration by apoptosis and autophagy-dependent cell death pathways in colorectal cancer
In conclusion, these findings demonstrate that the novel small-molecule activator of SIRT3 may hold a therapeutic potential as a drug candidate in colorectal cancer.PMID:38579616 | DOI:10.1016/j.bioorg.2024.107327 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - April 5, 2024 Category: Chemistry Authors: Yi Mou Yanmei Chen Zhichao Fan Liansong Ye Bing Hu Bo Han Guan Wang Source Type: research
Discovery of a novel class of rosmarinic acid derivatives as antibacterial agents: Synthesis, structure-activity relationship and mechanism of action
Bioorg Chem. 2024 Mar 28;146:107318. doi: 10.1016/j.bioorg.2024.107318. Online ahead of print.ABSTRACTTwenty-seven rosmarinic acid derivatives were synthesized, among which compound RA-N8 exhibited the most potent antibacterial ability. The minimum inhibition concentration of RA-N8 against both S. aureus (ATCC 29213) and MRSA (ATCC BAA41 and ATCC 43300) was found to be 6 μg/mL, and RA-N8 killed E. coli (ATCC 25922) at 3 μg/mL in the presence of polymyxin B nonapeptide (PMBN) which increased the permeability of E. coli. RA-N8 exhibited a weak hemolytic effect at the minimum inhibitory concentration. SYTOX Green assay, SEM...
Source: Bioorganic Chemistry - April 5, 2024 Category: Chemistry Authors: Yong Wang Zhiguang Liang Yihui Cao Cheung-Hin Hung Ruolan Du Alan Siu-Lun Leung Pui-Kin So Pak-Ho Chan Wing-Leung Wong Yun-Chung Leung Kwok-Yin Wong Source Type: research
Ferroptosis inducers: A new frontier in cancer therapy
Bioorg Chem. 2024 Apr 2;146:107331. doi: 10.1016/j.bioorg.2024.107331. Online ahead of print.ABSTRACTFerroptosis represents a non-apoptotic form of programmed cell death characterized by iron-dependent lipid peroxidation. This cell death modality not only facilitates the direct elimination of cancer cells, but also enhances their susceptibility to other pharmacological anti-cancer agents. The burgeoning interest in ferroptosis has been driven by a growing body of evidence that underscores the efficiency and minimal toxicity of ferroptosis inducers. Traditional inducers, such as erastin and RSL3 have shown substantial promi...
Source: Bioorganic Chemistry - April 5, 2024 Category: Chemistry Authors: Wenjing Ma Naiyuan Hu Wenqian Xu Linxi Zhao Chutong Tian Ken-Ichiro Kamei Source Type: research
Identification of benzo[b]thiophene-1,1-dioxide derivatives as novel PHGDH covalent inhibitors
Bioorg Chem. 2024 Apr 3;146:107330. doi: 10.1016/j.bioorg.2024.107330. Online ahead of print.ABSTRACTThe increased de novo serine biosynthesis confers many advantages for tumorigenesis and metastasis. Phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine biogenesis, exhibits hyperactivity across multiple tumors and emerges as a promising target for cancer treatment. Through screening our in-house compound library, we identified compound Stattic as a potent PHGDH inhibitor (IC50 = 1.98 ± 0.66 µM). Subsequent exploration in structural activity relationships led to the discovery of compound B12 that demon...
Source: Bioorganic Chemistry - April 5, 2024 Category: Chemistry Authors: Xin-Yu Cao Xinge Li Feng Wang Yichen Duan Xingmei Wu Guo-Qiang Lin Meiyu Geng Min Huang Ping Tian Shuai Tang Dingding Gao Source Type: research
