Article
Biochemistry & Molecular Biology
Tsz Tin Yu, Rajesh Kuppusamy, Muhammad Yasir, Md. Musfizur Hassan, Manjulatha Sara, Junming Ho, Mark D. P. Willcox, David StC. Black, Naresh Kumar
Summary: Peptidomimetics have emerged as a new class of antibacterial agents to combat drug-resistant bacteria. By incorporating hydrophobic and hydrophilic groups into a glyoxamide core, the synthesized compounds showed effective inhibition against Staphylococcus aureus and Escherichia coli biofilms without toxicity to human cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jie Wu, Tsz Tin Yu, Rajesh Kuppusamy, Md Musfizur Hassan, Amani Alghalayini, Charles G. Cranfield, Mark D. P. Willcox, David StC Black, Naresh Kumar
Summary: There is an urgent need for the development of new antibacterial agents to combat antibiotic resistance. Cholic acid-based small molecular antimicrobial peptide mimics show promise as potential new drugs for treating bacterial infections. Structure-activity relationship studies indicate that tryptophan moiety and a minimum of +2 charge are important for high antibacterial activity. Analogs containing lysine-like residues exhibit the highest antibacterial potency against Gram-positive S. aureus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ping Zeng, Lanhua Yi, Jiangtao Xu, Wei Gao, Chen Xu, Sheng Chen, Kin-Fai Chan, Kwok-Yin Wong
Summary: zp3 exhibited favorable bioactivity against Acinetobacter baumannii, inhibiting biofilm formation and eliminating preformed biofilm. It showed low cytotoxicity to mammalian cells and its bactericidal mode involved influencing ions balance and inducing membrane permeability alteration on Acinetobacter baumannii. In practical application, zp3 demonstrated good antibacterial activity on medical textiles.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Pharmacology & Pharmacy
Jong-Kook Lee, Soyoung Park, Young-Min Kim, Taeuk Guk, Min-Young Lee, Seong-Cheol Park, Jung Ro Lee, Mi-Kyeong Jang
Summary: This study identified a peptide with antifungal and antibiofilm effects as a potential agent against Candida albicans on contact lenses.
Article
Infectious Diseases
Ghayah Bahatheg, Rajesh Kuppusamy, Muhammad Yasir, David StC Black, Mark Willcox, Naresh Kumar
Summary: This study describes the development of short cationic peptoids with activity against Staphylococcus aureus strains from keratitis. The peptoids showed good antimicrobial activity against multiple strains, making them a promising class of antimicrobials.
Article
Infectious Diseases
Fahad M. Alsaab, Scott N. Dean, Shravani Bobde, Gabriel G. Ascoli, Monique L. van Hoek
Summary: In this study, a series of novel antimicrobial peptides (AMPs) named HRZN were designed using a computational approach to target multidrug-resistant Acinetobacter baumannii. HRZN-15 showed the highest antimicrobial activity and exhibited membrane permeabilization and depolarization. Further modification of HRZN-15 could lead to a new peptide with improved toxicity profile.
Article
Multidisciplinary Sciences
Abiodun Ogunsile, Nuttapon Songnaka, Somchai Sawatdee, Monthon Lertcanawanichakul, Sucheewin Krobthong, Yodying Yingchutrakul, Jumpei Uchiyama, Apichart Atipairin
Summary: Five novel anti-MRSA peptides were identified from Brevibacillus sp. STR19, with P2 showing the highest antimicrobial activity and causing membrane disruption. P2 exhibited activity against biofilm formation and eradication of tested pathogens, and showed no toxicity to human erythrocytes.
Article
Immunology
Huimin Duan, Xiangmin Zhang, Zhi Li, Jianrui Yuan, Fangwang Shen, Shicui Zhang
Summary: The study demonstrates the synergistic antibacterial effect between the AMP Pt5-1c derived from phosvitin and traditional antibiotics against multidrug-resistant bacteria. It also suggests the potential of using Pt5-1c to prolong the efficacy of certain antibiotics under threat of antibiotic resistance.
MICROBIAL PATHOGENESIS
(2021)
Article
Dentistry, Oral Surgery & Medicine
Yiyi Huang, Tingyu Wang, Yucong Chen, Huancai Lin, Dongru Chen
Summary: This study selected the most stable amyloid hexapeptide GIDLKI (GI6) to inhibit biofilm formation by multiple species of bacteria, including the cariogenic bacterium Streptococcus mutans. The results showed that GI6 effectively prevented and alleviated the development of dental caries without adverse effects on other organs in the body.
JOURNAL OF DENTISTRY
(2023)
Review
Microbiology
Robert E. W. Hancock, Morgan A. Alford, Evan F. Haney
Summary: This review discusses how the complex functional attributes of host defence peptides offer opportunities for antimicrobial therapeutics, with a focus on their emerging antibiofilm properties. The mechanisms of action of antibiofilm peptides are compared with antimicrobial peptides. Additionally, obstacles to translating candidate peptides into therapeutics and potential solutions are discussed.
NATURE REVIEWS MICROBIOLOGY
(2021)
Article
Medicine, Research & Experimental
Aaron P. Decker, Yajuan Su, Biswajit Mishra, Atul Verma, Tamara Lushnikova, Jingwei Xie, Guangshun Wang
Summary: This study investigates the effects of peptide stability on antimicrobial and antibiofilm activity and finds that peptide antimicrobial activity is critical for in vivo efficacy. Using a nanofiber/microneedle delivery device can protect peptides from degradation and provide a new approach for direct use of natural peptides or their cocktails for antimicrobial treatment.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biotechnology & Applied Microbiology
Yi Zhao, Xiao-yan Wang, Yan Sun, Zhi Li, Tao Liu, Qing-mei Liu, Jingyi Chen
Summary: B2CE-N26V5K, the most potent and nontoxic analog, was identified in this study. The results indicated that helicity promotes antibacterial activity, while the Rana box affects hemolytic activity.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2022)
Article
Chemistry, Medicinal
Yongzhi Chen, Hongxia Li, Jiayong Liu, Rongcui Zhong, Haizhou Li, Shanfang Fang, Shouping Liu, Shuimu Lin
Summary: The emergence of bacterial multidrug resistance and the lack of new antimicrobial agents have led to the urgent need for the discovery and development of novel antibacterials. Antimicrobial peptidomimetics have shown promise in overcoming antibiotic resistance and are effective in rapidly killing bacteria without inducing resistance. Specific compounds have demonstrated potent activity against Gram-positive bacteria, low toxicity to mammalian cells, good stability, and high efficacy in treating bacterial infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Food Science & Technology
Shen Yang, Zijin Yuan, Jude Juventus Aweya, Shanggui Deng, Wuyin Weng, Yueling Zhang, Guangming Liu
Summary: Bacteria contamination in Auricularia auricular culture bags can reduce yield and pose a risk to food safety. This study identified five species of bacteria in contaminated culture bags, including three species of Bacillus, Arthrobacter arilaitensis, and Staphylococcus warneri. A peptide called PvGBP2, derived from the beta-1,3-glucan-binding protein sequence of Penaeus vannamei, was found to have antimicrobial properties against Bacillus. PvGBP2 could inhibit the growth of Bacillus subtilis in the culture bags and prevent biofilm formation. Its mechanism of action involves perforating the cell wall and disrupting membrane integrity, leading to the leakage of intracellular solutes.
FOOD SCIENCE AND HUMAN WELLNESS
(2022)
Article
Pharmacology & Pharmacy
Jingru Shi, Chen Chen, Dejuan Wang, Ziwen Tong, Zhiqiang Wang, Yuan Liu
Summary: The study demonstrated that peptide WW307 displayed potent antibacterial activity against MDR bacteria, especially MRSA and Gram-negative pathogens carrying bla(NDM-5), mcr-1 or tet(X4). Additionally, WW307 showed great biofilm inhibition and eradication activity. Safety and stability experiments also indicated that WW307 had potential as a candidate for combating MDR pathogens.
Article
Biochemistry & Molecular Biology
Emma-Lucille Blayney, Milna Chennath, Charles G. Cranfield, Ronald J. Clarke
Summary: The Na+, K+-ATPase is an integral membrane protein that uses ATP hydrolysis to transport Na+ and K+ ions across the plasma membrane. It has essential roles in various physiological processes and is regulated through phosphorylation by protein kinase C (PKC) and Src kinase families. The study used the mirror tree method to analyze the coevolution between these kinases and Na+, K+-ATPase. The results suggested that the theta and eta isoforms of PKC and Src kinase are the most likely to interact with Na+, K+-ATPase. These findings will guide future experimental studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Michael Chhor, Esra Tulpar, Tara Nguyen, Charles G. Cranfield, Catherine A. Gorrie, Yik Lung Chan, Hui Chen, Brian G. Oliver, Lana McClements, Kristine C. McGrath
Summary: Cardiovascular disease (CVD) is a leading cause of death globally, with smoking being a major risk factor. Quitting smoking is challenging due to nicotine addiction and withdrawal symptoms. Electronic cigarettes (e-Cigs) have emerged as an alternative, but their cardiovascular effects are unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Infectious Diseases
Rajesh Kuppusamy, Muhammad Yasir, Tsz Tin Yu, Florida Voli, Orazio Vittorio, Michael J. Miller, Peter Lewis, David StC Black, Mark Willcox, Naresh Kumar
Summary: There is an urgent need for new antimicrobial agents to address the global increase in antibiotic resistance. This study focused on producing short amphiphilic antibacterial and antibiofilm agents by modifying the hydrophobic and cationic groups of anthranilamide peptidomimetics. The addition of a lysine cationic group at the tail position significantly enhanced activity against E. coli and reduced cytotoxicity against mammalian cells. These compounds demonstrated notable disruption of preformed biofilms of S. aureus at micromolar concentrations.
Article
Nanoscience & Nanotechnology
Upeksha Mirissa Lankage, Stephen A. Holt, Samara Bridge, Bruce Cornell, Charles G. Cranfield
Summary: This study introduces a sparsely tethered triglyceride substrate for the impedance sensing of lipase activity in real time. The substrate can form an anchored bilayer off the gold electrode, allowing for ion transport through membrane defects caused by enzymatic hydrolysis. The rapid and reliable detection method has potential applications in disease studies, monitoring of lipase production, and point-of-care diagnostics.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Biochemistry & Molecular Biology
Katrina Browne, Rajesh Kuppusamy, William R. Walsh, David StC Black, Mark D. P. Willcox, Naresh Kumar, Renxun Chen
Summary: Antibiotic resistance is a global challenge, and combination therapies using antibiotics and antimicrobial peptidomimetics can mitigate the development of resistance in bacteria. This strategy demonstrates synergistic activity against both Gram-positive and Gram-negative bacteria and has significant potential in clinical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Anuja Dahal, Kamal Shrestha, Rashmi Karki, Saraswati Bhattarai, Shiva Aryal, Satish Kumar Deo, Balmukunda Regmi, Mark Willcox, Shyam Kumar Mishra
Summary: This study analyzed the antibiotic sensitivity and biofilm-forming ability of urinary tract infection strains from renal disease patients. The results showed that the most common uropathogens in renal disease patients were Escherichia coli, Klebsiella pneumoniae, and Enterococcus spp. Some antibiotics such as amikacin, meropenem, and cefoperazone-sulbactam were effective against Gram-negative bacteria, while doxycycline, nitrofurantoin, and tetracycline were effective against Gram-positive bacteria. Additionally, most strains were capable of forming biofilms, and 70.8% were multidrug-resistant. Therefore, aminoglycoside, carbapenem, beta-lactam combination agents, and nitrofuran group of antibiotics may be the optimal first-line empirical therapies for uropathogens in hospitalized renal disease patients. Regular surveillance of resistance patterns and the study of biofilm formation in uropathogens are important for effective management of the patients.
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
(2023)
Article
Chemistry, Physical
Sudip Chakraborty, Georgio Katsifis, Iman Roohani, Cyrille Boyer, David McKenzie, Mark D. P. Willcox, Renxun Chen, Naresh Kumar
Summary: This study demonstrates the efficacy of an antibacterial polymer as a coating material for hydroxyapatite and glass surfaces, which are widely used in orthopedics and biomedical sciences. Both physical and covalent attachment modes of the polymer to the material surfaces were explored. The modified surfaces showed significant antibacterial activity against Gram-negative bacterium E. coli, and the activity persisted for a prolonged period on the covalently modified materials' surfaces.
Article
Crystallography
Christopher E. Marjo, Anne M. Rich, Mohan M. Bhadbhade, Saroj Bhattacharyya, Songyan Yin, David M. Miskovic, Vina R. Aldilla, Naresh Kumar
Summary: This study investigates a layered crystal system with hydrogen-bonded chloro-s-triazine rings functionalised with alkyl or fluoroalkyl chains. The results show that the crystal undergoes a thermally-induced phase transition when substituted with N-propyl chains, but the phase transition is successfully suppressed when replaced with fluorinated N-propyl chains. The study also suggests that short-chain fluoroalkanes can exert strong control over the assembly and stability of an organic crystal.
Article
Biochemistry & Molecular Biology
Floriana Cappiello, Sudhir Verma, Xiao Lin, Isabel Y. Moreno, Bruno Casciaro, Debarun Dutta, Alison M. McDermott, Mark Willcox, Vivien J. Coulson-Thomas, Maria Luisa Mangoni
Summary: The corneal epithelium is essential for both vision and immune defense. Corneal abrasion can lead to severe eye infections, but recent research has discovered peptides that not only treat keratitis but also promote corneal wound healing, which could have potential clinical applications.
Article
Infectious Diseases
Sahil Shandil, Tsz Tin Yu, Shekh Sabir, David StC. Black, Naresh Kumar
Summary: As bacteria develop resistance against antimicrobials, alternative methods to tackle this issue must be developed. In this study, quinazolinone inhibitors were designed using molecular docking to target the pqs system in P. aeruginosa. Compound 6b showed the highest pqs inhibitory activity and no bacterial growth inhibition.
Review
Infectious Diseases
Shakeel Shahzad, Mark D. P. Willcox, Binod Rayamajhee
Summary: The global rise in antibiotic resistance in bacteria has become a major challenge in treating infectious diseases. This literature review aims to decipher the evolving mechanisms of resistance to polymyxins among clinically significant pathogens. Understanding these mechanisms may help develop suitable methods for detecting polymyxin resistance determinants and the development of novel antimicrobial molecules.
Article
Infectious Diseases
Umme Laila Urmi, Samuel Attard, Ajay Kumar Vijay, Mark D. P. Willcox, Naresh Kumar, Salequl Islam, Rajesh Kuppusamy
Summary: The development of potent antiviral agents is crucial for combating viral infections worldwide. In this study, the antiviral potential of 17 peptidomimetic compounds was evaluated against MHV-1 and HSV-1. Compounds 11 and 14 showed the most potent inhibitory effects, and they were found to directly influence the viral envelope. These findings suggest that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.
Article
Materials Science, Multidisciplinary
Zeyu Shao, Karen Hakobyan, Jiangtao Xu, Renxun Chen, Naresh Kumar, Mark Willcox, Edgar H. H. Wong
Summary: This study reports the development of a smart antimicrobial polymer that can be activated under UV light to exhibit antimicrobial activity. The polymer showed bacteriostatic and bactericidal effects against multidrug-resistant bacteria, as well as the ability to disrupt bacterial membranes and kill biofilms. Furthermore, the polymer effectively killed cancer cells, demonstrating its potential in cancer therapy.
ACS APPLIED POLYMER MATERIALS
(2023)
Meeting Abstract
Biophysics
Ronald J. Clarke, Bogdan Lev, Milna Chennath, Toby W. Allen, Charles G. Cranfield, Emma-Lucille Blayney, Flemming Cornelius
BIOPHYSICAL JOURNAL
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
