Article
Biochemistry & Molecular Biology
Zesheng Hao, Bin Yu, Wei Gao, Haoyin Chen, Dongyan Yang, You Lv, Yue Zhang, Lei Chen, Zhijin Fan
Summary: Twenty-one novel pyrazole-thiazole carboxamide derivatives were synthesized and evaluated for their fungicidal activities, with compounds 6d and 6j showing promising results both in vitro and in vivo, particularly compound 6j demonstrating good protective activity against Rhizoctonia solani and Puccinia sorghi Schw.
MOLECULAR DIVERSITY
(2022)
Article
Biochemistry & Molecular Biology
Ruta Minickaite, Birute Grybaite, Rita Vaickelioniene, Povilas Kavaliauskas, Vidmantas Petraitis, Ruta Petraitiene, Ingrida Tumosiene, Ilona Jonuskiene, Vytautas Mickevicius
Summary: Thiazole derivatives have been widely studied for their pharmacological effects. This research aimed to explore the antiviral, antioxidant, and antibacterial activities of novel thiazole compounds. The results showed that different substituents on the thiazole ring exhibited cytotoxicity, antiviral activity, antioxidant activity, and antibacterial activity. Structure optimization of the novel thiazole compounds could potentially lead to the development of compounds with targeted antiviral activity against influenza A.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Physical
Sraa Abu-Melha
Summary: The thiadiazole-pyrazole hybrid 3 was synthesized and used to produce four thiadiazole-pyrazole compounds 5 and 6a-c. The configuration and energetic properties of the hybrids were studied, revealing a small energy gap and a specific sorting order. The synthesized thiadiazole-pyrazole hybrids exhibited significant antitumor activities and binding appropriateness with caspase-3 enzyme.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Agriculture, Multidisciplinary
Meng Li, Weiwei Wang, Xiang Cheng, Yunxiao Wang, Yao Chen, Jiexiu Gong, Xihao Chang, Xianhai Lv
Summary: In this study, a series of pyrazole carboxamide thiazole derivatives were designed, synthesized, and evaluated for their antifungal activities against plant pathogens. The bioassay results showed that several compounds exhibited good antifungal activities, with compounds 6i and 19i showing better efficacy than the control drug. Compound 23i also displayed significant inhibitory activity against a potato pathogen. Scanning electron microscopy analyses revealed that compound 6i could disrupt the surface morphology of the target fungus.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Meenakshi Duhan, Rahul Singh, Meena Devi, Jayant Sindhu, Rimpy Bhatia, Ashwani Kumar, Parvin Kumar
Summary: In this study, novel alpha-amylase inhibitors in the form of pyrazole clubbed thiazole hybrids were synthesized, with compounds 4g and 4h showing the highest inhibition rates at 50 μg/mL. QSAR models and docking simulations were used to understand the binding interactions and mechanisms responsible for the activity of these compounds against alpha-amylase.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Chemistry, Multidisciplinary
Raghavender Matta, Jalapathi Pochampally, Bala Narsimha Dhoddi, Shankar Bhookya, Sampath Bitla, Anjini Gayatri Akkiraju
Summary: A series of biologically active triazole and pyrazole compounds containing 2,4-disubstituted thiazole analogues were synthesized and identified. Compounds 12e, 12f, and 12k showed the highest antimicrobial activity and exhibited strong binding affinity with S. aureus topoisomerase IV enzyme. These compounds also demonstrated remarkable antioxidant activity.
Article
Chemistry, Multidisciplinary
Di Zhao, Yanying Liu, Yang Li, Yu Chen
Summary: A green synthesis of 4-ferrocenylthiazole derivatives was successfully achieved using a deep eutectic solvent without the use of volatile organic solvents. The synthetic strategy exhibited mild reaction conditions, simple operation, and high yields. Moreover, the newly-synthesized compounds showed significant antibacterial activities.
Article
Chemistry, Medicinal
Chungsik Kim, Mintesinot Kassu, Kenneth P. Smith, James E. Kirby, Roman Manetsch
Summary: A total of 20 novel derivatives of compound KP-40 containing Pyrazole-thiazole core were designed and synthesized through traditional SAR analysis. Four of the compounds showed significant adjunctive potential with improved solubility, and key physicochemical properties for the development of active Gram-negative antibacterials were revealed through further analysis using PEMPO algorithm. Consideration of PEMPO scores prior to synthesis of analogs may be a simple yet effective strategy in conjunction with traditional SAR approaches for designing potent Gram-negative antibacterials.
Article
Agriculture, Multidisciplinary
Dongguo Xia, Xiang Cheng, Xiaohang Liu, Chengqi Zhang, Yunxiao Wang, Qiaoyun Liu, Qi Zeng, Niqian Huang, Yao Cheng, Xianhai Lv
Summary: Novel pyrazole carboxylate derivatives containing a flexible thiazole backbone were successfully synthesized and evaluated for their antifungal bioactivities. Compound 24 showed excellent bioactivities against Botrytis cinerea and Sclerotinia sclerotiorum, while compound 15 exhibited remarkable antifungal activity against Valsa mali. Compounds 3, 15, and 24 are promising antifungal candidates worthy of further fungicide development.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ruo-Mei Rui, Cheng-Run Tang, Chun-Tao Zhang, Wen-Kai Pan, Kai Gan, Rong-Hua Luo, Zi-Qian Wei, Fan-Shun Jing, Si-Ming Huang, Liu-Meng Yang, Yi-Ming Li, Yue-Ping Wang, Wei-Lie Xiao, Hong-Bing Zhang, Yong-Tang Zheng, Yan-Ping He
Summary: Both HIV and DENV pose serious threats to human life, health, and the social economy. However, no successful vaccines have been developed for either. This study developed novel compounds with potent anti-HIV and anti-DENV activity, and discussed the impact of C-6 substituents on their activity.
BIOORGANIC CHEMISTRY
(2022)
Review
Chemistry, Physical
Atamjit Singh, Danish Malhotra, Karanvir Singh, Renu Chadha, Preet Mohinder Singh Bedi
Summary: Thiazole derivatives are important heterocycles in medicinal chemistry, with widespread biological activities. This review summarizes recent advancements in the medicinal chemistry of thiazole derivatives, including marketed drugs, therapeutic candidates, synthesis methods, biological significances, and structure-activity relationships.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemistry & Molecular Biology
Fang Liu, Xiao Cao, Tao Zhang, Li Xing, Zhiling Sun, Wei Zeng, Hui Xin, Wei Xue
Summary: In this study, a series of derivatives were synthesized by introducing the pharmacophore pyrazole ring and piperazine ring into the structure of myricetin. The structures of the compounds were determined using high-resolution mass spectrometry. The compounds were tested for their bioactivity against bacteria and fungi, showing significant activity against Xoo and Phomopsis sp. The mechanism of action and impact on cell membrane were also investigated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Abrar Bayazeed, Rua B. Alnoman, Kahdr Alatawi, Omar M. Alatawi, Alaa M. Alqahtani, Mariam Mojally, Noof A. Alenazi, Nashwa M. El-Metwaly
Summary: Several new thiazole derivatives linked pyrazole and/or pyridine rings were synthesized and optimized. The thiazole-pyridine hybrids 8 and 9 exhibited high cytotoxicity against the MCF-7 cell line. Docking study showed strong binding of these hybrids to HER2.
JOURNAL OF SAUDI CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Alia Abdulaziz Alfi, Arwa Alharbi, Jihan Qurban, Matokah M. Abualnaja, Hana M. Abumelha, Fawaz A. Saad, Nashwa M. El-Metwaly
Summary: In this study, the phenoxyacetamide moiety was used as a link bridge for the synthesis of novel pyrazole-integrated thiazole derivatives. The synthesized compounds were subjected to geometric optimization and activity evaluation using computational methods.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Multidisciplinary
Alexei N. Izmest'ev, Galina A. Gazieva, Lada V. Anikina, Sergey A. Pukhov, Valentina A. Karnoukhova, Natalya G. Kolotyrkina, Angelina N. Kravchenko
Summary: Two novel series of compounds were synthesized and evaluated for their antiproliferative activity, with one compound showing high potency with very low GI(50) values against a subset of cancer cell lines among 60 tested.
NEW JOURNAL OF CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Iwona E. Glowacka, Katarzyna Gawron, Dorota G. Piotrowska, Mirthe Graus, Graciela Andrei, Dominique Schols, Robert Snoeck, Anita Camps, Emiel Vanhulle, Kurt Vermeire
Summary: In this study, a series of 48 hybrids were synthesised and evaluated for antiviral activity. The hybrids contained a diethoxyphosphoryl group connected to the triazole moiety via ethylene or propylene linker, and substituted benzyl or benzoyl function in the quinazoline-2,4-dione moiety. The hybrids showed potent antiviral activities against Respiratory Syncytial Virus (RSV), with some weak activity against varicella zoster virus and human cytomegalovirus.
ANTIVIRAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Shenghua Gao, Letian Song, Yusen Cheng, Fabao Zhao, Dongwei Kang, Shu Song, Mianling Yang, Bing Ye, Wei Zhao, Yajie Tang, Erik De Clercq, Christophe Pannecouque, Peng Zhan, Xinyong Liu
Summary: The study found that Indolylarylsulfones (IASs) have potent antiviral activity against HIV-1 but high cytotoxicity. To address this issue, researchers synthesized a compound called R10L4 with reduced cytotoxicity and significant inhibitory activity against wild-type and mutant strains of HIV-1. The results suggest that R10L4 may be a promising non-nucleoside reverse transcriptase inhibitor.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Biochemistry & Molecular Biology
M. P. Paramonova, E. S. Gureeva, A. A. Ozerov, R. Snoeck, G. Andrei, D. A. Aleksandrov, A. L. Khandazhinskaya, M. S. Novikov, S. N. Kochetkov
Summary: A new series of 1-[ω-(bromophenoxy)alkyl]-uracil derivatives containing various fragments were synthesized and tested for their antiviral activity against human cytomegalovirus. It was found that the compound with a bridge of five methylene groups exhibited high anti-cytomegalovirus activity in vitro.
DOKLADY BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Immunology
Hanna Helena Schalkwijk, Aspasia Georgala, Sarah Gillemot, Arturo Temblador, Dimitri Topalis, Sebastian Wittnebel, Graciela Andrei, Robert Snoeck
Summary: This study conducted long-term follow-up of a patient with immunodeficiency before and after stem cell transplantation, revealing the evolution and frequent reactivation of herpes simplex virus 1 strains. The multidrug resistance phenotype of a novel DNA polymerase mutation was confirmed by gene editing. This research is important for understanding virus evolution and drug resistance mutations in immunodeficient patients.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Chemistry, Medicinal
Ya-Li Sang, Christophe Pannecouque, Erik De Clercq, Shuai Wang, Fen-Er Chen
Summary: A series of novel biphenyl-DAPY derivatives were developed using the fragment-hopping strategy to enhance the anti-resistance efficacy of a non-nucleoside reverse transcriptase inhibitor (NNRTI). Most of the compounds exhibited improved anti-HIV-1 potency, with compound 8r showing exceptional potency against wild-type HIV-1 and mutant strains. The new DAPY analogue had lower cytotoxicity, higher selectivity index, and favorable pharmacokinetic properties, making it a potential candidate for HIV treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Zhao Wang, Prem Prakash Sharma, Brijesh Rathi, Minghui Xie, Erik De Clercq, Christophe Pannecouque, Dongwei Kang, Peng Zhan, Xinyong Liu
Summary: This study discovered a series of novel tetrahydropyrido[4,3-d]pyrimidine derivatives with broad-spectrum antiviral activity and improved resistance profiles against NNRTI-resistant variants. The most potent inhibitor 10c exhibited desirable physicochemical properties and in vitro metabolic stability. It also showed lower cytochrome P450 inhibition and human ether-a-go-go-related gene blockade liability compared to currently available medications.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Tom Vermeyen, Aliou M. Balde, Wouter A. Herrebout, Johan Neyts, Christophe Pannecouque, Luc Pieters, Emmy Tuenter
Summary: This study investigated the bioactive constituents of Hymenocallis littoralis and identified three previously undescribed compounds, as well as six known compounds. Some of these compounds showed weak inhibitory activity against SARS-CoV-2 at non-cytotoxic concentrations. Furthermore, a preliminary structure-activity relationship for lycorine-type alkaloids in anti-SARS-CoV-2 activity was explored, suggesting the importance of ring C.
Article
Chemistry, Medicinal
Hao Song, Yu Xia, Tao Zhang, Caiyun Dun, Bairu Meng, Erik De Clercq, Christophe Pannecouque, Dongwei Kang, Peng Zhan, Xinyong Liu
Summary: In order to develop more effective HIV-1 inhibitors against various NNRTIs-resistant strains, a series of 5-cyano substituted diarylpyridines were designed based on cocrystal structural analysis. Among them, compound I-5b exhibited the highest potency (EC50 = 5.62-171 nM) against wild-type and mutant HIV-1 strains. Particularly for the K103 N strain, I-5b showed exceptional activity with an EC50 value of 9.37 nM, surpassing NVP (EC50 = 5128 nM) and EFV (EC50 = 114 nM), and comparable to ETR (EC50 = 3.45 nM). Furthermore, all compounds were found to target HIV-1 RT with moderate RT enzyme inhibitory activity (IC50 = 0.094-12.0 & mu;M). The binding mode of representative compounds with RT was elucidated through molecular docking.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Polina Kamzeeva, Ivan Petushkov, Ekaterina Knizhnik, Robert Snoeck, Yuri Khodarovich, Ekaterina Ryabukhina, Vera Alferova, Artur Eshtukov-Shcheglov, Evgeny Belyaev, Julia Svetlova, Tatiana Vedekhina, Andrey Kulbachinskiy, Anna Varizhuk, Graciela Andrei, Andrey Aralov
Summary: Emerging and re-emerging viruses cause global outbreaks and epidemics, highlighting the need for new antiviral drugs. Researchers synthesized and evaluated nucleoside analogs and their derivatives, finding that one compound had antiviral activity against coronaviruses and specifically inhibited biocondensate formation important for replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Evert Cleenders, Priyanka Koshy, Elisabet Van Loon, Katrien Lagrou, Kurt Beuselinck, Graciela Andrei, Marta Crespo, Katrien De Vusser, Dirk Kuypers, Evelyne Lerut, Kris Mertens, Olga Mineeva-Sangwo, Parmjeet Randhawa, Aleksandar Senev, Robert Snoeck, Ben Sprangers, Claire Tinel, Amaryllis Van Craenenbroeck, Jan van den Brand, Marc Van Ranst, Geert Verbeke, Maarten Coemans, Maarten Naesens
Summary: This study aimed to investigate the value of performing a biopsy at the time of BKPyV-DNAemia in distinguishing presumptive and proven PyVAN. The results showed that plasma viral load had good predictive value for SV40 positivity, while the dichotomy of SV40 immunohistochemistry did not predict viral clearance. Therefore, the distinction between presumptive and proven PyVAN based on SV40 immunohistochemistry has limited clinical value.
KIDNEY INTERNATIONAL
(2023)
Article
Plant Sciences
Ngoc-Thao-Hien Le, Steven De Jonghe, Kristien Erven, Johan Neyts, Christophe Pannecouque, Tom Vermeyen, Wouter A. Herrebout, Luc Pieters, Emmy Tuenter
Summary: Scadoxus multiflorus is traditionally used for respiratory problems and this study investigated its alkaloidal composition. A previously undescribed alkaloid and fourteen known ones were identified. Some of the alkaloids exhibited weak antiviral activity against SARS-CoV-2, highlighting the potential of S. multiflorus as a source for anti-SARS-CoV-2 Amaryllidaceae alkaloid scaffolds.
PHYTOCHEMISTRY LETTERS
(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)
