Article
Biochemistry & Molecular Biology
Balint Lorinczi, Peter Simon, Istvan Szatmari
Summary: This study presents a new synthesis method for triarylmethane derivatives containing two biologically potent skeletons through the Mannich reaction. It may contribute to the synthesis of new neuroprotective compounds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sara Janowska, Sylwia Andrzejczuk, Piotr Gawrys, Monika Wujec
Summary: A series of novel Mannich bases were synthesized and evaluated for their antimicrobial activity against bacteria and yeasts. The compounds exhibited significant activity against Gram-positive bacteria, including staphylococci, as well as selected strains of Gram-negative bacteria. They also showed high fungistatic activity against Candida spp. yeasts. In addition, in silico studies suggested that the tested compounds have good oral bioavailability. Overall, these findings provide valuable data for further research on these compounds.
Article
Biochemistry & Molecular Biology
Lamya H. Al-Wahaibi, Ahmed A. B. Mohamed, Samar S. Tawfik, Hanan M. Hassan, Ali A. El-Emam
Summary: A series of novel N-Mannich base compounds were synthesized in this study, with the piperazinomethyl derivatives showing broad-spectrum antibacterial activities. Some compounds also demonstrated potent anti-proliferative activity against Gram-positive bacteria and various cancer cell lines.
Article
Chemistry, Organic
Gulsah Karakaya, Aysun Ozdemir, Asli Ture, Berrin Ozcelik, Mutlu Aytemir
Summary: Dermatophytes are pathogenic fungi that cause superficial fungal infections. Current antifungal drugs have drawbacks, leading to the need for new antidermatophyte agents.
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2022)
Article
Chemistry, Applied
Min He, Meiyan Fan, Wenjing Liu, Yongjun Li, Guangcheng Wang
Summary: The study identified 4d as a potent tyrosinase inhibitor with copper-chelating ability, low cytotoxicity, and significant antibrowning effects. These compounds may serve as lead molecules for developing novel tyrosinase inhibitors and antibrowning agents.
Review
Dermatology
Julia Capp Zilles, Francielli Lima dos Santos, Irene Clemes Kulkamp-Guerreiro, Renata Vidor Contri
Summary: Kojic acid and its derivatives present a variety of applications for human use, including depigmentation, antioxidant, antimicrobial, anti-inflammatory, radioprotective, anticonvulsant, and obesity management activities. The depigmentation activity is attributed to their binding to tyrosinase active site, regulation of melanogenesis factors, leucocytes modulation, and free radical scavenging. They also exhibit cytotoxicity to certain cancer cell lines. In terms of safety, they are considered safe for human use at tested concentrations. Kojic acid and its derivatives hold great potential for cosmetic, pharmaceutical, and medical applications.
EXPERIMENTAL DERMATOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Anjali K. Gopalakrishnan, Shanty A. Angamaly, Mohanan P. Velayudhan
Summary: Imidazole, a heterocycle containing two non-adjacent nitrogen atoms, is widely utilized in medical and clinical fields due to its affinity with bio receptors and enzymes. Organic molecules with imidazole derivatives play an important role in pharmaceuticals, particularly in drug development.
Article
Chemistry, Physical
Klaudia Karkeszova, Maria Mastihubova, Vladimir Mastihuba
Summary: The study demonstrates that kojic acid esters can be produced by various enzymes with different regioselectivity, with pig pancreatic lipase showing distinct stereo selectivity in the reaction.
Article
Chemistry, Physical
Yuhao Chen, Zhonghua Chen, Yaowen Zhuo
Summary: New Mannich bases, MPO and MPPO, were synthesized and studied as corrosion inhibitors for N80 steel in 1 M HCl solution. The results showed that MPO and MPPO exhibited significant corrosion inhibition efficiency at higher concentrations, and the mechanism of inhibition was determined through various tests.
Review
Chemistry, Medicinal
Cem Yamali, Mustafa Gul, Halise Inci Gul
Summary: A multitude of Mannich bases have been synthesized and evaluated for their potential therapeutic applications, showing enhanced biological activity and altered physicochemical properties of drug candidates.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Kiran S. Dalal, Mangal A. Chaudhari, Dipak S. Dalal, Bhushan L. Chaudhari
Summary: A novel biosynthetic route for the synthesis of kojic acid derivatives was developed efficiently with the use of lipase from Aspergillus niger, achieving high conversion rates (82-95%) in aqueous medium. The lipase was reused for three consecutive cycles without significant loss of activity, indicating the potential of this bioprocess to replace chemical catalytic processes.
CATALYSIS COMMUNICATIONS
(2021)
Article
Microbiology
Tianming Chen, Ziming Chen, Yuzhen Li, Bin Zeng, Zhe Zhang
Summary: In this study, a novel MFS transporter, Aokap4, was identified to be involved in the production of kojic acid. Deletion of Aokap4 affected the hyphal growth, conidial production, and biomass of A. oryzae. Aokap4 was required for heat- and cell-wall-stress tolerance but not oxidative and osmotic stress. This study expands our understanding of the biological roles of MFS transporters and provides a foundation for further research on kojic acid synthesis in A. oryzae.
Article
Biochemistry & Molecular Biology
Saeed Babaee, Gholamabbas Chehardoli, Tahmineh Akbarzadeh, Mohammad Ali Zolfigol, Mohammad Mahdavi, Arezoo Rastegari, Farshad Homayouni Moghadam, Zahra Najafi
Summary: A novel series of tacrine-based derivatives were synthesized and evaluated as anti-cholinesterase agents, with cyclopentapyranopyridine-kojic acid derivatives showing slightly better AChE inhibitory activity. Compound 6f displayed the highest anti-AChE activity and is considered a promising AChE inhibitor for the treatment of Alzheimer's disease.
CHEMISTRY & BIODIVERSITY
(2021)
Article
Chemistry, Multidisciplinary
Sushant Aryal, Christopher A. Hone, Matthew I. J. Polson, Daniel J. Foley
Summary: We report a single-step enantioselective synthesis of 5-monosubstituted hydantoins via condensation of glyoxals and ureas in the presence of a chiral phosphoric acid at room temperature. The products were obtained in up to 99% yield and 98:2 enantiomeric ratio. Mechanistic and kinetic studies revealed that the reaction likely proceeds via face-selective protonation of an enol-type intermediate.
Article
Chemistry, Multidisciplinary
Evgeny Buravlev, Oksana G. Shevchenko
Summary: A series of C-3-aminomethyl derivatives based on alizarin were synthesized using Mannich reaction. The compounds exhibited superior radical scavenging activity and Fe2+-chelation ability compared to alizarin. They demonstrated significant antioxidant activity in biologically relevant test systems, including inhibition of lipid oxidation and protection of red blood cells under acute oxidative stress conditions. The Mannich base containing a thiomorpholinomethyl moiety showed the highest activity.
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)