Article
Chemistry, Multidisciplinary
Galina F. Makhaeva, Igor Serkov, Nadezhda Kovaleva, Elena Rudakova, Natalia P. Boltneva, Ekaterina A. Kochetkova, Alexey N. Proshin, Sergey O. Bachurin
Summary: The novel conjugates synthesized in this study exhibit potential anti-cholinesterase activity and antioxidant efficacy, with compounds containing aminoalkyl spacers showing better esterase profile and antioxidant effects.
MENDELEEV COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Yun-Peng Xie, Nagarajan Sangaraiah, Jiang-Ping Meng, Cheng-He Zhou
Summary: Novel carbazole-oxadiazoles were developed as potential antibacterial agents and showed predominant inhibitory effects on both Gram-positive and -negative bacteria, especially in impeding the growth of MRSA and Pseudomonas aeruginosa ATCC 27853. The compounds exhibited low cytotoxicity and low tendency to develop resistance, and could disintegrate bacterial cell membranes to exert excellent antibacterial effects.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Siddappa A. Patil, Shivaputra A. Patil, Ever A. Ble-Gonzalez, Stephen R. Isbel, Sydney M. Hampton, Alejandro Bugarin
Summary: This review discusses various carbazole derivatives and their antimicrobial activity, providing valuable references for medicinal chemists in their search for new approaches to combat microbial infections, which are a leading cause of death worldwide.
Article
Biochemistry & Molecular Biology
Galina F. F. Makhaeva, Nadezhda V. V. Kovaleva, Elena V. V. Rudakova, Natalia P. P. Boltneva, Maria V. V. Grishchenko, Sofya V. V. Lushchekina, Tatiana Y. Y. Astakhova, Olga G. G. Serebryakova, Elena N. N. Timokhina, Ekaterina F. F. Zhilina, Evgeny V. V. Shchegolkov, Mariya V. V. Ulitko, Eugene V. V. Radchenko, Vladimir A. A. Palyulin, Yanina V. V. Burgart, Victor I. I. Saloutin, Sergey O. O. Bachurin, Rudy J. J. Richardson
Summary: The conjugates of tacrine and salicylamide with varied structure of the salicylamide fragment and salicylic aldehyde derivatives showed broad-spectrum biological activity. These hybrids exhibited potent inhibition towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity towards BChE. The most active compounds were salicylimine derivatives, which showed potential to block AChE-induced beta-amyloid aggregation. These synthesized conjugates are promising multifunctional agents for the potential treatment of AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Galina F. Makhaeva, Sofya V. Lushchekina, Nadezhda V. Kovaleva, Tatiana Yu. Astakhova, Natalia P. Boltneva, Elena V. Rudakova, Olga G. Serebryakova, Alexey N. Proshin, Igor V. Serkov, Tatiana P. Trofimova, Victor A. Tafeenko, Eugene V. Radchenko, Vladimir A. Palyulin, Vladimir P. Fisenko, Jan Korabecny, Ondrej Soukup, Rudy J. Richardson
Summary: Eleven new amiridine-piperazine hybrids were synthesized as potential agents for Alzheimer's disease treatment, displaying mixed-type reversible inhibition of AChE and BChE. Compounds with para-substituted aromatic moieties exhibited the highest anti-AChE activity, while compounds with cyclohexyl and 2-MeO-Ph groups showed appreciable antioxidant capability. The conjugates showed low activity against carboxylesterase and exhibited potential to block AChE-induced beta-amyloid aggregation.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Liping Jiang, Bo Liu, Shengjie Hou, Tiande Su, Qiyun Fan, Eman Alyafeai, Yaqin Tang, Mengqi Wu, Xiaohua Liu, Jing Li, Yu Hu, Wulan Li, Zhiwei Zheng, Yuan Liu, Jianzhang Wu
Summary: This study synthesized chalcone derivatives and found that half of them exhibited good anti-Toxoplasma activity, with four compounds showing potent anti-T. gondii activity and low cytotoxicity. These findings provide promising compounds for the development of anti-Toxoplasma agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Tyler D. Weinhold, Natalie A. Reece, Kevin Ribeiro, Maredh Lopez Ocasio, Noelle Watson, Kenneth Hanson, Ashley R. Longstreet
Summary: The electron-donating capabilities of carbazoles have sparked interest in their use as photoinduced single-electron reductants. By manipulating the structure, a better understanding of their reactivity and broader application scope can be achieved. In this study, eight carbazole derivatives were synthesized, characterized, and evaluated as single-electron photoreductants in the hydrodehalogenation of aryl halides and arylation of N-methylpyrrole.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Olmo Martin-Camara, Marina Arribas, Geoffrey Wells, Marcos Morales-Tenorio, Angeles Martin-Requero, Gracia Porras, Ana Martinez, Giorgio Giorgi, Pilar Lopez-Alvarado, Isabel Lastres-Becker, J. Carlos Menendez
Summary: Hybrid compounds containing structural fragments of the Rho kinase inhibitor fasudil and the NRF2 inducers caffeic and ferulic acids were designed, and one of the compounds showed good antioxidant properties and tolerability. This compound was able to induce the NRF2 signature and promote the expression of antioxidant response enzymes. The study suggests the therapeutic potential of this compound for ALS patients, particularly those with a SOD1 mutation.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
H. Pavan Kumar, H. K. Kumara, R. Suhas, D. Channe Gowda
Summary: A new small library of molecules containing bis-urea/thiourea pendants in lysine conjugated to three different heterocycles has been synthesized and shown to exhibit potent antimicrobial activity. The presence of urea/thiourea, substituent, and heterocycle is found to be crucial for exerting strong biological effects, with isoxazole being particularly beneficial. Docking studies have demonstrated exceptional binding efficiency for some of the active compounds, indicating their potential as drug candidates for microbial-related diseases.
ARCHIV DER PHARMAZIE
(2021)
Article
Infectious Diseases
Fan-Fei Meng, Ming-Hao Shang, Wei Wei, Zhen-Wu Yu, Jun-Lian Liu, Zheng-Ming Li, Zhong-Wen Wang, Jian-Guo Wang, Huan-Qin Dai
Summary: MRSA is a global health threat and new antibacterial agents are urgently needed. In this study, 21 novel sulfonylurea derivatives were designed and synthesized, and nine compounds showed inhibitory activities against MRSA. Compound 9i and 9q exhibited the lowest minimum inhibitory concentrations against MRSA, surpassing the positive controls vancomycin and methicillin. This is the first time that sulfonylurea derivatives have been identified as promising inhibitors against different MRSA clinical isolates. Additionally, all the synthesized compounds showed minimal inhibitory concentrations greater than 100μg/mL against Candida albicans.
Article
Chemistry, Medicinal
Maria Grishchenko, Galina F. Makhaeva, Yanina Burgart, Elena Rudakova, Natalia P. Boltneva, Nadezhda Kovaleva, Olga G. Serebryakova, Sofya Lushchekina, Tatiana Y. Astakhova, Ekaterina F. Zhilina, Evgeny Shchegolkov, Rudy J. Richardson, Victor Saloutin
Summary: New conjugates of tacrine and salicylamide with alkylene spacers were synthesized and evaluated for their potential as anti-AD agents. The compounds demonstrated high inhibitory activities against cholinesterases and showed potential to block AD-related protein aggregation.
Article
Chemistry, Multidisciplinary
Salma Fares, Walaa M. M. El Husseiny, Khalid B. Selim, Mohammed A. M. Massoud
Summary: To develop potential treatments for Alzheimer's disease (AD) and explore the effect of chromene group, 35 new tacrine-chromene derivatives were designed, synthesized, and evaluated. Compounds 5c and 5d showed strong inhibitory activity against AD-related targets such as hAChE, BuChE, BACE-1, and MAO-B, as well as antioxidant properties and metal-chelating abilities. They also demonstrated acceptable safety profiles and BBB penetrability. These compounds have the potential to be promising candidates for the development of multifunctional drugs against AD.
Article
Chemistry, Medicinal
Noura S. Hanafy, Nada A. A. M. Aziz, Sanadelaslam S. A. El-Hddad, Mohamed A. Abdelgawad, Mohammed M. Ghoneim, Amal F. Dawood, Samy Mohamady, Khaled El-Adl, Sahar Ahmed
Summary: Novel thiazolidine-2,4-diones were developed and evaluated as dual inhibitors of EGFR(T790M) and VEGFR-2 against multiple cancer cell lines. Compounds 6a, 6b, and 6c demonstrated significant activity against HCT116, MCF-7, A549, and HepG2 cells. Although not as potent as sorafenib, they exhibited higher efficacy than erlotinib. These compounds also showed promising effects on VEGFR-2 and EGFR(T790M), with 6b and 6c being the most effective derivatives. Additionally, compounds 6a, 6b, and 6c exhibited favorable in silico computed ADMET profiles.
ARCHIV DER PHARMAZIE
(2023)
Article
Chemistry, Medicinal
Zhongcheng Cao, Xianwu Fu, Xingyue Wang, Tianlong Zhang, Lei Zhong, Qian Xia, Jiang Zhu
Summary: A series of 2-hydroxyl-4-benzyl-xybenzyl aniline derivatives were designed, synthesized, and evaluated as novel multifunctional agents for Parkinson's disease treatment. The screening showed that compound 6h exhibited excellent MAO-B inhibition, high antioxidant activity, good metal chelating ability, BBB permeability, and significant neuroprotective effect. Moreover, compound 6h effectively alleviated neuroinflammation and improved dopamine levels in MPTP-induced Parkinson's disease mice, making it a promising candidate for further development against PD.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Stephy Elza John, Anamika Sharma, Shivani Gulati, Darshana Bora, Nagula Shankaraiah
Summary: In modern medicinal chemistry, a molecular hybridization approach was used to design and synthesize a new class of cis-stilbene-based 1,2,4-triazole/1,3,4-oxadiazole conjugates. These conjugates exhibited promising cytotoxicity against selected human cancer cell lines, with cis-stilbene-based 1,2,4-triazole conjugate 5a being the most effective against the A549 cell line. Mechanistic analysis revealed that 5a induced apoptosis, DNA damage, nuclear morphological changes, and ROS generation, and exhibited G2/M phase arrest and tubulin polymerization inhibition. Additionally, 5a showed no toxicity towards normal cells and demonstrated significant anti-cancer activity.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
E. Shchegolkov, N. P. Boltneva, Ya Burgart, S. Lushchekina, O. G. Serebryakova, N. A. Elkina, E. Rudakova, A. N. Perminova, G. F. Makhaeva, V. Saloutin
Summary: This study improved the synthetic procedure for a compound and established its structure. The esterase profile of the compound showed no inhibition against cholinesterase and high activity against carboxylesterase. Additionally, the compound exhibited strong radical-scavenging effect.
RUSSIAN CHEMICAL BULLETIN
(2022)
Article
Biochemistry & Molecular Biology
Galina F. F. Makhaeva, Nadezhda V. V. Kovaleva, Elena V. V. Rudakova, Natalia P. P. Boltneva, Maria V. V. Grishchenko, Sofya V. V. Lushchekina, Tatiana Y. Y. Astakhova, Olga G. G. Serebryakova, Elena N. N. Timokhina, Ekaterina F. F. Zhilina, Evgeny V. V. Shchegolkov, Mariya V. V. Ulitko, Eugene V. V. Radchenko, Vladimir A. A. Palyulin, Yanina V. V. Burgart, Victor I. I. Saloutin, Sergey O. O. Bachurin, Rudy J. J. Richardson
Summary: The conjugates of tacrine and salicylamide with varied structure of the salicylamide fragment and salicylic aldehyde derivatives showed broad-spectrum biological activity. These hybrids exhibited potent inhibition towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity towards BChE. The most active compounds were salicylimine derivatives, which showed potential to block AChE-induced beta-amyloid aggregation. These synthesized conjugates are promising multifunctional agents for the potential treatment of AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Taisiya A. Antonenko, Yulia A. Gracheva, Dmitry B. Shpakovsky, Mstislav A. Vorobyev, Dmitrii M. Mazur, Victor A. Tafeenko, Yury F. Oprunenko, Elena F. Shevtsova, Pavel N. Shevtsov, Alexey A. Nazarov, Elena R. Milaeva
Summary: A series of novel organotin(IV) complexes based on 2-(N-3 ',5 '-di-tert-butyl-4'-hydroxyphenyl)-iminomethylphenol (L) were synthesized and characterized. The crystal structures of L and complex 2 were determined. The complexes exhibited antioxidant, antiproliferative, and apoptosis-inducing activities.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vyacheslav E. Semenov, Irina Zueva, Sofya Lushchekina, Eduard G. Suleimanov, Liliya M. Gubaidullina, Marina M. Shulaeva, Oksana A. Lenina, Konstantin A. Petrov
Summary: Novel derivatives based on 6-methyluracil and condensed uracil with terminal meta- and para-benzoate moieties in polymethylene chains were synthesized. They showed potential in decreasing beta-amyloid plaques and treating memory impairment in an Alzheimer's disease transgenic model.
Article
Biochemistry & Molecular Biology
Yanina V. V. Burgart, Natalia A. A. Elkina, Evgeny V. V. Shchegolkov, Olga P. P. Krasnykh, Galina F. F. Makhaeva, Galina A. A. Triandafilova, Sergey Yu. Solodnikov, Natalia P. P. Boltneva, Elena V. V. Rudakova, Nadezhda V. V. Kovaleva, Olga G. G. Serebryakova, Mariya V. V. Ulitko, Sophia S. S. Borisevich, Natalia A. A. Gerasimova, Natalia P. P. Evstigneeva, Sergey A. A. Kozlov, Yuliya V. V. Korolkova, Artem S. S. Minin, Anna V. V. Belousova, Evgenii S. S. Mozhaitsev, Artem M. M. Klabukov, Victor I. I. Saloutin
Summary: 4-Arylhydrazinylidene-5-(polyfluoroalkyl)pyrazol-3-ones (4-AHPs) were successfully synthesized and showed acceptable ADME profile. Varying the substituents in 4-AHPs allowed for changes in their biological activity, including anticarboxylesterase action, antioxidant properties, anti-cancer activity, and inhibition of bacterial growth. Some 4-AHPs also exhibited cell visualization capabilities and analgesic effects, while a mechanism involving blocking the TRPV1 receptor was proposed for their antinociceptive action.
Article
Biochemistry & Molecular Biology
Yulia Aleksandrova, Aldar Munkuev, Evgenii Mozhaitsev, Evgenii Suslov, Dmitry Tsypyshev, Kirill Chaprov, Roman Begunov, Konstantin Volcho, Nariman Salakhutdinov, Margarita Neganova
Summary: Novel monoterpene-based hydroxamic acids were synthesized, consisting of compounds with a hydroxamate group directly bound to monoterpene scaffolds or connected through aliphatic or aromatic linkers. Some of these compounds showed powerful HDAC6 inhibitory activity, with a hexa- and heptamethylene linker and (-)-perill fragment exhibiting the most excellent activity. Moderate antiradical activity was also observed. Compounds with an aromatic linker based on para-substituted cinnamic acids demonstrated the ability to suppress aggregation of beta-amyloid peptide 1-42. The lead compound 35a showed neuroprotective effects on in vivo Alzheimer's disease models. This research suggests the potential use of monoterpene-derived hydroxamic acids in Alzheimer's disease treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Alexander M. M. Efremov, Olga V. V. Beznos, Roman O. O. Eremeev, Natalia B. B. Chesnokova, Elena R. R. Milaeva, Elena F. F. Shevtsova, Natalia A. A. Lozinskaya
Summary: This article presents an efficient method for synthesizing novel 2-oxindole derivatives using microwave-assisted decarboxylative condensation. The compounds were found to regulate intraocular pressure and show potential antiglaucomic activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Valentina Echeverria, Cristhian Mendoza, Alex Iarkov
Summary: The survival of animals depends on their cognitive abilities, such as learning and memory, to adapt to the environment. Cotinine, a cholinergic modulator, has various beneficial effects, including neuroprotection, antidepressant, anti-inflammatory, antioxidant, and memory-enhancing effects. It exerts its positive effects on cognition by modulating the alpha 7-nicotinic acetylcholine receptors (nAChRs) and inhibiting toll-like receptors (TLRs). These receptors play a crucial role in brain functions, including neurotransmission and neuroinflammation. Understanding the mechanisms of memory formation and the actions of Cotinine in aging and neurological diseases is discussed in this article.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Yulia Aleksandrova, Margarita Neganova
Summary: The relationship between oncological pathologies and neurodegenerative disorders is complex and has become a topic of interest among researchers. Recent scientific evidence suggests that various factors and processes contribute to the development of these diseases, revealing an intriguing connection between oncology and neurodegeneration. This review explores the links between oxidative stress, epigenetic dysregulation, and metabolic dysfunction in detail, and discusses the potential therapeutic approaches in current research. This comprehensive analysis helps in the development of advanced diagnostic tools and innovative pharmacological strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Ivan M. Veselov, Daria V. Vinogradova, Andrey V. Maltsev, Pavel N. Shevtsov, Elena A. Spirkova, Sergey O. Bachurin, Elena F. Shevtsova
Summary: This review focuses on the common features connecting metabolic disorders and type 2 diabetes with the development of Alzheimer's disease. The pathogenesis of Alzheimer's disease overlaps with the mechanisms of type 2 diabetes, and aging is an important risk factor for both diseases. Common pathological mechanisms include oxidative stress, neuroinflammation, insulin resistance, and amyloidosis, as well as mitochondrial dysfunctions and cell death. The available drugs for type 2 diabetes and Alzheimer's disease have limited efficacy, highlighting the need for new treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Multidisciplinary
S. O. Bachurin, A. Yu. Aksinenko, G. F. Makhaeva, E. F. Shevtsova
Summary: A strategy for designing potential drugs for neurodegenerative diseases is discussed, which involves combining multiple structural moieties of neuroactive substances within a single molecule. Synthetic approaches to these compounds are considered and exemplified by the synthesis of conjugates of specific moieties linked through spacers. The biological activity of the compounds, including their effects on enzyme systems, receptors, mitochondrial structures, microtubule systems, and antioxidant properties, is evaluated. The results provide new opportunities for the design of highly efficient multitarget drugs, as evidenced by the selection of leading compounds that have passed preclinical trials.
RUSSIAN CHEMICAL BULLETIN
(2023)
Article
Biochemistry & Molecular Biology
Maria A. Lapshina, Elena F. Shevtsova, Vladimir V. Grigoriev, Aleksey Yu. Aksinenko, Aleksey A. Ustyugov, Daniil A. Steinberg, Grigoriy V. Maleev, Elena S. Dubrovskaya, Tatiana V. Goreva, Tatiana A. Epishina, Vladimir L. Zamoyski, Galina F. Makhaeva, Vladimir P. Fisenko, Ivan M. Veselov, Daria V. Vinogradova, Sergey O. Bachurin
Summary: The study aims to modify the structural core of the Edaravone-phenylpyrazolone moiety and combine it with aminoadamantane pharmacophore to expand its action against the pathogenesis of ALS. New conjugates of edaravone derivatives with 1-aminoadamantanes were synthesized, showing inhibitory effects on lipid peroxidation, calcium-related mitochondrial permeability, and CNS neuronal currents, as well as reducing aggregation of mutated FUS-protein. These findings are significant for the development of new drugs for the treatment of ALS.
