Article
Biochemistry & Molecular Biology
Guler Yagiz, Samir Abbas Ali Noma, Aliye Altundas, Khattab Al-khafaji, Tugba Taskin-Tok, Burhan Ates
Summary: This study synthesized various triazole derivatives under green chemistry conditions and investigated their inhibition properties on xanthine oxidase activity. The results showed promising inhibition activities of certain derivatives against XO enzyme, with good correlation between docking scores and IC50 values. These findings provide a promising start for the development of novel and potent XO inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
M. S. Raghu, K. Yogesh Kumar, M. K. Prashanth, V. S. Anusuya Devi, Fahd Alharethy, Byong-Hun Jeon
Summary: We developed a series of pyrazolo[1,5-a][1,3,5]triazine derivatives (5a-l) through condensation, intramolecular ring annulation, and acylation processes. These compounds exhibited moderate to substantial antioxidant activity and were effective in inhibiting LOX and XO enzyme activity. Particularly, compound 5f showed excellent antioxidant and enzyme inhibition abilities. Molecular docking studies further confirmed the correlation between docking scores and experimental antioxidant and enzyme inhibition activity.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Spectroscopy
Hongyan Du, Shu Jie Li
Summary: This study revealed the interaction mechanism between Porphyra polysaccharide (PP) and Xanthine oxidase (XO), demonstrating that PP reversibly inhibits XO activity through hydrophobic interactions and induces changes in its secondary structure and conformation. Molecular docking further revealed that PP inserted into the hydrophobic cavity of XO, leading to the inhibition of its activity.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2022)
Article
Agriculture, Multidisciplinary
Zhipeng Yu, Ruotong Kan, Sijia Wu, Hui Guo, Wenzhu Zhao, Long Ding, Fuping Zheng, Jingbo Liu
Summary: The study identified a novel tetrapeptide, EEAK, from tuna protein with high XO inhibitory activity, which binds to pivotal residues of XO's active sites through conventional hydrogen bond interactions and electrostatic interactions. This suggests that EEAK could serve as a potential candidate for treating gout and hyperuricemia.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2021)
Article
Biochemistry & Molecular Biology
Xiaofen Qi, Haoran Chen, Kaifang Guan, Yue Sun, Rongchun Wang, Qiming Li, Ying Ma
Summary: In this study, XO inhibitory peptides were identified from whey protein isolate hydrolysates, and their inhibitory mechanism and in vivo activities were investigated. The peptides interacted with residues around the active site of XO and exhibited anti-hyperuricemia effects. These findings suggest that these peptides can be considered as natural XO inhibitors for the treatment of HUA.
BIOORGANIC CHEMISTRY
(2022)
Article
Food Science & Technology
Xueqin Wang, Zhenzhen Cui, Yuan Luo, Yu Huang, Xinbin Yang
Summary: This study investigates the inhibitory effect of sodium kaempferol-3'-sulfonate (KS) on xanthine oxidase (XO) and its therapeutic potential for hyperuricemia. The results show that KS effectively inhibits XO activity and reduces serum uric acid levels, as well as alleviating renal damage. These findings suggest that KS may serve as a potent XO inhibitor for hyperuricemia-related diseases.
FOOD AND CHEMICAL TOXICOLOGY
(2023)
Article
Chemistry, Medicinal
Kristin M. Reiland, Todd J. Eckroat
Summary: Polymethylene-linked isatin dimers and 3-indolyl-3-hydroxy-2-oxindole dimers were synthesized as selective BChE inhibitors, with the best compounds showing significant inhibitory activity and moderate blood-brain barrier permeability. These compounds exhibited selectivity towards BChE and demonstrated potential as lead compounds for further exploration.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Applied
Qiang Zhao, Xiao Jiang, Zhenjie Mao, Jingjing Zhang, Jianan Sun, Xiangzhao Mao
Summary: This study successfully separated and purified the enzymatic lysate of oyster protein using ultrafiltration and molecular exclusion chromatography. Three novel peptides with strong XO inhibitory activity were identified through LC-MS/MS and molecular docking technology. The mechanism of action between the peptides and XO was revealed, and the structure of the peptides was rationally designed based on this information.
Article
Agriculture, Multidisciplinary
Zhenjie Mao, Hong Jiang, Xiangzhao Mao
Summary: In this study, 17 novel XO inhibitory peptides were isolated from pacific white shrimp or swimming crab, and Ala-Glu-Ala-Gln-Met-Trp-Arg (AEAQMWR) exhibited the strongest inhibitory activity. Molecular docking results demonstrated that attractive charge, salt bridge, and hydrogen bond played a crucial role in the interactions between XO inhibitory peptides and the pivotal residues of Arg880, Glu802, and Glu1261. Additionally, XO inhibitory peptides alleviated hyperuricemia by inhibiting inflammation and preventing increased uric acid transporter expression levels.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Antonella Fais, Francesca Pintus, Benedetta Era, Sonia Floris, Amit Kumar, Debapriyo Sarmadhikari, Valeria Sogos, Eugenio Uriarte, Shailendra Asthana, Maria Joao Matos
Summary: The coumarin scaffold shows promise in the development of bioactive agents, and this study focuses on the synthesis and evaluation of hydroxylated 3-arylcoumarins for their XO inhibition and antioxidant properties. Compound 11 is found to be the most potent XO inhibitor, and both compounds 11 and 5 show mixed-type inhibition and good antioxidant activity. Molecular docking studies correlate the theoretical and experimental binding affinity to the XO binding pocket.
Article
Food Science & Technology
Jiahong Xie, Haoxin Cui, Yang Xu, Lianghua Xie, Wei Chen
Summary: The study identified delphinidin-3-O-sambubioside as a potent XO inhibitor with high inhibitory activity and the ability to induce conformational changes in XO, preventing substrate entry into the active pocket.
FOOD QUALITY AND SAFETY
(2021)
Article
Chemistry, Applied
Zhenjie Mao, Hong Jiang, Jianan Sun, Xiangzhao Mao
Summary: In this study, molecular docking and BLAST were used to rapidly screen and optimize XO inhibitory peptides from Pacific white shrimp. Seven new peptides were identified, and YNITGW showed the strongest activity. Insertion of Trp residue enhanced the inhibitory activity. This study demonstrated that molecular docking is a novel and feasible method for obtaining bio-active peptides.
Article
Biochemistry & Molecular Biology
Aya Y. Rashad, Shaymaa E. Kassab, Hoda G. Daabees, Ahmed E. Abdel Moneim, Sherif A. F. Rostom
Summary: Various febuxostat derivatives were synthesized and evaluated for their inhibitory activities on XO and COX enzymes. Some of these compounds showed potential in vitro anti-inflammatory and hypouricemic activities, with superior binding profiles to the active sites compared to existing drugs.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Tamer El Malah, Hanaa Farag, Bahaa A. Hemdan, Randa E. Abdel Mageid, Mohamad T. Abdelrahman, May A. El-Manawaty, Hany F. Nour
Summary: Antibiotic resistance poses a severe threat to humanity, prompting researchers to synthesize a series of isatin-1,2,3-triazole hybrids and evaluate their antimicrobial activity. The most active derivative displayed stronger activity against Gram-negative bacteria and showed potential for binding to specific enzymes via various interactions.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Applied
Ummi Liyana Mohamad Rodzi, Amalina Mohd Tajuddin, Siti Syaida Sirat, Nur Azzalia Kamaruzaman, Nageswara Rao Meroshine, El Hassane Anouar, Karimah Kassim
Summary: This study synthesized new complexes and characterized their structures using various methods. In silico methodology was employed to explore their anticancer properties and interactions. The results showed that these complexes have potential anticancer activities and can serve as candidate drugs.
APPLIED ORGANOMETALLIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Atamjit Singh, Kirandeep Kaur, Harneetpal Kaur, Pallvi Mohana, Saroj Arora, Neena Bedi, Renu Chadha, Preet Mohinder Singh Bedi
Summary: A series of triazole tethered isatin-benzotriazole hybrids were designed and synthesized as potential antifungal agents against Candida strains. Among the synthesized hybrids, AS14 showed the most potent activity against fluconazole resistant Candida albicans. Structure-activity relationship studies revealed the optimal substitutions for inhibitory potential of the structure against Candida albicans. AS14 was also able to inhibit biofilm formation and ergosterol synthesis in Candida albicans, and molecular docking and dynamic studies supported its effectiveness and stability. Overall, AS14 can serve as a promising lead for the development of potent and safer antifungal agents for Candida infections.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Biochemistry & Molecular Biology
Nitish Kumar, Aanchal Khanna, Komalpreet Kaur, Harmandeep Kaur, Anchal Sharma, Preet Mohinder Singh Bedi
Summary: The emergence of antimicrobial resistance poses a significant threat to the human population due to a lack of development in new antimicrobial agents. Therefore, it is essential to conduct research and develop new novel antimicrobial agents. This review discusses rational approaches, design strategies, structure-activity relationships, and mechanistic insights of newly developed quinoline derivatives as antimicrobial agents.
MOLECULAR DIVERSITY
(2023)
Article
Chemistry, Applied
Nitish Kumar, Ankita Rajput, Harmandeep Kaur, Anchal Sharma, Kavita Bhagat, Jatinder Vir Singh, Saroj Arora, Preet Mohinder Singh Bedi
Summary: This study investigates the XO inhibitory potential of biologically active Alkannin/Shikonin (A/S) derivatives and confirms their efficacy through in vitro experiments and pharmacophore hypothesis.
NATURAL PRODUCT RESEARCH
(2023)
Review
Biotechnology & Applied Microbiology
Harneetpal Kaur, Atamjit Singh, Kirandeep Kaur, Ajay Kumar, Shivani Attri, Farhana Rashid, Sharabjit Singh, Neena Bedi, Hardeep Singh Tuli, Shafiul Haque, Khalil Alkuwaity, Hanaa M. M. Tashkandi, Steve Harakeh, Saroj Arora
Summary: Multidrug resistance (MDR) is a major barrier in treating breast cancer, but a combination of 4-MTBITC-PTX can significantly enhance the apoptosis pathway in T-47D cells, indicating its clinical application for breast cancer treatment. The combination has a synergistic antiproliferative activity and promotes the production of reactive oxygen species (ROS) while reducing mitochondrial membrane potential. Mechanistic studies also show that the combination arrests T-47D cells in the G(2)/M phase and increases late apoptotic cell population. Moreover, it decreases the protein level of Bcl-xl and increases the levels of p53, cleaved caspase-3, and cleaved caspase-9.
BIOTECHNOLOGY AND GENETIC ENGINEERING REVIEWS
(2023)
Article
Microbiology
Kirandeep Kaur, Atamjit Singh, Rajanbir Kaur, Harneetpal Kaur, Rajinder Kaur, Saroj Arora, Neena Bedi
Summary: In recent years, fungal infections, particularly candidiasis caused by Candida albicans, have become increasingly common and have resulted in significant mortality and morbidity, especially in immunocompromised patients. Shikonin, a natural naphthazarin derivative, has shown promising antifungal efficacy, however, its mechanism of action is still not fully understood. Therefore, this study aimed to investigate the molecular mechanism behind the anti-candida efficacy of shikonin through in vitro experiments and in situ molecular modeling studies. The study utilized qualitative and quantitative techniques including minimum inhibitory concentration assays, time kill assays, cell cycle analysis, apoptotic assays, static biofilm formation assays, microscopic biofilm assessment assays, ergosterol content estimation, and molecular docking/simulation studies. The findings demonstrated a significant effect of shikonin against Candida albicans, particularly in inhibiting biofilm formation. The increasing concentration of shikonin led to candidal cell apoptosis and necrosis, indicating a dose-dependent effect. Furthermore, it was found that shikonin exhibited fungicidal activity likely through complexation with ergosterol, which was supported by molecular docking and simulation studies.
ARCHIVES OF MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Atamjit Singh, Karanvir Singh, Aman Sharma, Kirandeep Kaur, Renu Chadha, Preet Mohinder Singh Bedi
Summary: Fungal infections are becoming a serious threat to the healthcare system due to the increased resistance to currently available antifungal drugs. Azoles have been the most effective and commonly used antifungal agents, but their side effects and emerging resistance have prompted the need for new and potent antifungal agents. This review focuses on azole and non-azole derivatives that target fungal lanosterol 14a-demethylase (CYP51) as potential antifungal agents. The review provides insights into the structure-activity relationship, pharmacological outcomes, and molecular interactions of these derivatives with CYP51, aiming to assist medicinal chemists in designing rational and effective antifungal agents to combat emerging drug resistance.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Review
Biochemistry & Molecular Biology
Atamjit Singh, Karanvir Singh, Aman Sharma, Kaustubh Joshi, Brahmjeet Singh, Sambhav Sharma, Kevin Batra, Kirandeep Kaur, Dilpreet Singh, Renu Chadha, Preet Mohinder Singh Bedi
Summary: Candida infections, particularly caused by Candida albicans, pose a significant threat to immunocompromised and hospitalized patients, with increasing resistance to antifungal drugs. The 1,2,3-triazole nucleus has gained importance in the development of antifungal drugs, with numerous studies focusing on its utilization against Candida albicans. This review provides insights into preclinical studies, clinical trials, and newly approved drugs, discussing the structure-activity relationship and future perspectives for the design and development of potent antifungal agents.
CHEMISTRY & BIODIVERSITY
(2023)
Review
Chemistry, Physical
Atamjit Singh, Karanvir Singh, Aman Sharma, Komalpreet Kaur, Kirandeep Kaur, Renu Chadha, Preet Mohinder Singh Bedi
Summary: Diabetes mellitus is a global metabolic disorder affecting 422 million people and causing severe complications. Current antidiabetic drugs are ineffective, necessitating the development of novel agents. Alpha-glucosidase inhibitors have shown promise due to their synergistic potency, safety, and competitive inhibition. Medicinal chemists have designed structural hybrids and heterocycles to improve the binding affinity and potency of these inhibitors. This article summarizes recent research on alpha-glucosidase inhibitors, providing insights into their pharmacology, structure-activity relationships, mechanisms, and in silico studies. It will be valuable for researchers in designing potent antidiabetic agents.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Cell Biology
Atamjit Singh, Karanvir Singh, Aman Sharma, Sambhav Sharma, Kevin Batra, Kaustubh Joshi, Brahmjeet Singh, Kirandeep Kaur, Renu Chadha, Preet Mohinder Singh Bedi
Summary: Breast cancer is a common and difficult-to-manage disease with high mortality and morbidity rates, posing a significant threat to mankind and healthcare systems. In 2020, there were 2.3 million diagnosed cases of breast cancer and it caused 685,000 deaths globally, highlighting the severity of the disease. The relapse of cases, drug resistance, and associated side effects further worsen the situation. Therefore, there is an urgent need to develop potent and safer antibreast cancer agents.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Shivani Attri, Ajay Kumar, Kirandeep Kaur, Prabhjot Kaur, Sanha Punj, Neena Bedi, Hardeep Singh Tuli, Saroj Arora
Summary: The aim of this study was to evaluate the anti-psoriatic potential of bakuchiol loaded solid lipid nanoparticles (SLNs) by modulating inflammatory and oxidative pathways. Bak-loaded SLNs were prepared and characterized. The release studies confirmed sustained release of Bak-SLNs-based gel. In a UV-B-induced psoriatic rat model, Bak showed significant anti-psoriatic effect via regulating inflammatory markers and levels of antioxidant enzymes. RT-qPCR analysis confirmed the downregulation of inflammatory markers by Bak. The study indicates that Bak-loaded SLNs-based gel can be a novel therapeutic approach for psoriasis.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Atamjit Singh, Karanvir Singh, Jashandeep Kaur, Ramanpreet Kaur, Aman Sharma, Jasleen Kaur, Uttam Kaur, Renu Chadha, Preet Mohinder Singh Bedi
Summary: Alzheimer's disease, the most prevalent form of dementia worldwide, currently lacks effective treatment options. This review focuses on the pathogenesis of the disease and the development of 1,2,3-triazole containing derivatives as potential anti-Alzheimer's agents. The review provides insight into established targets of the disease and discusses the design, structure-activity relationships, and pharmacological outcomes of multifunctional anti-Alzheimer's agents containing 1,2,3-triazole. It serves as a baseline for future research groups working on Alzheimer's drug development.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Atamjit Singh, Kirandeep Kaur, Pallvi Mohana, Karanvir Singh, Aman Sharma, Jignesh Prajapati, Dweipayan Goswami, Neha Khosla, Uttam Kaur, Rajanbir Kaur, Rajinder Kaur, Abhineet Rana, Sandeep Kour, Puja Ohri, Saroj Arora, Renu Chadha, Preet Mohinder Singh Bedi
Summary: This research reports the design, synthesis, and antibacterial activity of a novel series of triazole tethered thymol-isatin hybrids. Most of the hybrids exhibited a broad-spectrum antibacterial efficacy against standard human pathogenic as well as clinically isolated multidrug-resistant bacterial strains. Among them, hybrid compound AS8 showed the most effective antibacterial activity against MRSA, including biofilm inhibitory potential. AS8 also exhibited dehydrosqualene synthase inhibitory potential in MRSA and decreased the production of virulence factor staphyloxanthin. Furthermore, AS8 was found to be non-toxic and showed potent in vivo antibacterial efficacy as well as a modulated immune response.
RSC MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Atamjit Singh, Karanvir Singh, Aman Sharma, Kirandeep Kaur, Renu Chadha, Preet Mohinder Singh Bedi
Summary: Xanthine oxidase plays a crucial role in diseases like gout, and there is a need for the development of novel inhibitors. This review provides important information on design strategies, structural insights, and pharmacological output, suggesting fragment-based drug design and molecular hybridization as suitable methods for development.
RSC MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Physical
Atamjit Singh, Karanvir Singh, Aman Sharma, Jasleen Kaur, Ramanpreet Kaur, Jashandeep Kaur, Kirandeep Kaur, Renu Chadha, Preet Mohinder Singh Bedi
Summary: MRSA is a significant bacterial pathogen with resistance to many antibiotics, necessitating the development of new drugs. The 1,2,3-triazole nucleus is an important tool for developing effective anti-MRSA agents.
JOURNAL OF MOLECULAR STRUCTURE
(2024)
