Article
Chemistry, Multidisciplinary
Suresh Snoxma Smile, Mohanakumaran Athira, Gurusamy Harichandran, Ponnusamy Shanmugam
Summary: A highly functionalized 9,9-disubstituted (phenylethynyl)-fluorene-appended N-methyl-7-azaindole derivatives were successfully synthesized from various fluorene propargylic alcohols and substituted-7-azaindoles using BF3OEt2 as a catalyst. The reaction scope was demonstrated by selecting different fluorene propargylic alcohols and substituting 7-azaindoles. A plausible reaction mechanism involving propargylic carbocation was proposed. The synthetic transformation of the products was demonstrated through Suzuki coupling and Click reaction. The synthesized compounds exhibited blue emissive properties in terms of photophysical properties such as absorption, solvatochromism, emission, and Stokes shift.
Article
Biochemistry & Molecular Biology
Qingfei Meng, Xue Ren, Rui Wang, Yu Han, Xiufen Li, Qin Zhang, Zhenpeng Li, Yuexing Wang, Longjiang Huang, Haibo Yu
Summary: A series of 3(1,2,3,6-tetrahydropyridine)-7-azaindole derivatives were synthesized and evaluated for their anticonvulsant activities and neurotoxicity. Compounds 4i, 4p, and 5k showed significant anticonvulsant activities in the PTZ-induced epilepsy model, but not in the MES model. These compounds also exhibited lower neurotoxicity. The presence of a N-atom at the 7-position of the 7-azaindole and a double-bond in the 1,2,3,6-tetrahydropyridine skeleton were found to be essential for the antiepileptic activities.
BIOORGANIC CHEMISTRY
(2023)
Article
Plant Sciences
Masashi Yokoya, Miku Yamazaki-Nakai, Keiyo Nakai, Natchanun Sirimangkalakitti, Supakarn Chamni, Khanit Suwanborirux, Naoki Saito
Summary: In this study, a useful intramolecular photoredox transformation of 7-methoxy-6-methyl-1,2,3,4-tetrahydroisoquinoline-5,8-dione tricyclic models into 5-hydroxy-tetrahydroisoquinol[1,3]dioxoles in excellent yields is described. This methodology was applied to the transformation of renieramycin M into renieramycins T and S and the transformation of saframycin A. The results of cytotoxicity studies are also presented.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Qin Zhang, Xintao Gao, Xiyu Duan, Han Liang, Mingyuan Gao, Dianquan Dong, Chuanlong Guo, Longjiang Huang
Summary: This study designed and synthesized a series of novel 7-azaindole derivatives and evaluated their antitumor activity in human lung cancer cells. The results showed that compounds 4a and 5j exhibited significant anti-proliferative activity and good inhibition on Erk5 kinase.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Chaojie Wang, Fengming He, Ke Sun, Kaiqiang Guo, Sheng Lu, Tong Wu, Xiang Gao, Meijuan Fang
Summary: This study identified a compound called G7a that inhibits the infection of SARS-CoV-2. Through molecular simulations and experimental validations, it was confirmed that G7a binds to the virus and cell receptors, thereby preventing viral invasion. This finding holds potential for the development of novel therapeutics against SARS-CoV-2.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Haifeng Wang, Jing Li, Jie Qin, Jie Li, Yishen Chen, Dongliang Song, Haishan Zeng, Shuang Wang
Summary: In this study, confocal Raman microspectroscopy was used to investigate the cellular response of cisplatin in osteosarcoma cells. Results showed that nucleic acids were the main components affected, and detailed analysis was provided through multivariate analysis and imaging techniques.
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
(2022)
Review
Chemistry, Organic
Jian-Qing Zhang, Xiao-Yu Xu, Shu-Qiang Cao, You-Quan Zou
Summary: This review summarizes the research progress of AIEgens nanoprobes bearing benzobisthiadiazole derivatives in the NIR-II region and discusses the recent advances in bioimaging and photodynamic therapy, as well as the challenges in this field.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Meng Yin, Yongsheng Fang, Xiaotong Sun, Minggao Xue, Caimei Zhang, Zhiyun Zhu, Yamiao Meng, Lingmei Kong, Yi Yi Myint, Yan Li, Jingfeng Zhao, Xiaodong Yang
Summary: Three series of podophyllotoxin derivatives were synthesized with various nitrogen-containing heterocycles. The antitumor activity of these derivatives was evaluated against human tumor cell lines in vitro. The results showed that podophyllotoxin-imidazolium salts and podophyllotoxin-1,2,4-triazolium salts a1-a20 exhibited excellent cytotoxic activity, with a6 being the most potent compound. Podophyllotoxin-1,2,3-triazole derivatives b1-b5 showed medium cytotoxic activity, while podophyllotoxin-amine compounds c1-c3 displayed good cytotoxic activity. Further experiments revealed that compound a6 induced G2/M cell cycle arrest and apoptosis in HCT-116 cells.
FRONTIERS IN CHEMISTRY
(2023)
Article
Chemistry, Organic
Jialiang Qin, Mingji Ke, Deji Cuo, Shangping Xin, Yongbo Xue, Ruoting Zhan, Huicai Huang
Summary: Here, we report a novel synthetic method for the benzylation of 1H-benzotriazole amides with methyl coumalate using DBU as the catalyst, leading to the synthesis of stilbenes and biaryl derivatives. The synthesized novel compounds exhibited potent anti-proliferative and anti-invasive activities against H1299 cells.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Leandro Marcos Santos, Nelson Jose Freitas da Silveira
Summary: Fragment-based drug discovery is a powerful paradigm in medicinal chemistry and is widely practiced by researchers in academia and industry. Azaindoles, particularly the 7-azaindole, are extensively used as molecular fragments in pharmaceutical innovation projects, and they are present in the chemical structure of approved antitumor drugs and therapeutic candidates.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Chengbin Yang, Mingzhu Lu, Yi Chen, Ruiqing Xiang, Tianze Qiu, Yu Jia, Yongtai Yang, Xiaofeng Liu, Mingli Deng, Yun Ling, Yaming Zhou
Summary: Breast cancer is the cancer with the highest incidence globally, and the newly designed 7-azaindole derivatives FD2054 and FD2078 are potent PI3K inhibitors with promising antiproliferative activity against MCF-7 and MDA-MB-231 breast cancer cell lines, showing potential as candidates for anticancer drug development.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Mona A. Alamri, Mutlaq Al-Jahdali, Najlaa S. Al-Radadi, Mostafa A. Hussien
Summary: Three new triazene compounds with different substituents were synthesized and characterized, showing good DNA binding and cytotoxic activities, especially one compound exhibiting strong inhibition against both cell lines. Molecular docking studies indicated good correlations between compound binding and experimental cytotoxicity findings.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Pharmacology & Pharmacy
Jiahui Ye, Longfei Mao, Luoyijun Xie, Rongjun Zhang, Yulin Liu, Lizeng Peng, Jianxue Yang, Qingjiao Li, Miaomiao Yuan
Summary: Theophylline derivative compound d17 demonstrates strong antiproliferative activity against a variety of cancer cells, particularly the NSCLC cell lines H460 and A549. By altering the Bax/Bcl-2 ratio and downregulating phosphorylated Akt protein expression, compound d17 significantly induces cell apoptosis and shows minimal toxicity to normal hepatocytes.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yangyang Liu, Dongsheng Zhao, Chenghua Zhang, Hui Fang, Qingsitong Shen, Zhixian Wang, Jiangying Cao
Summary: Aminopeptidase N (APN) inhibitors, particularly pyrazoline-based hydroxamate derivatives, have shown significant potential as antitumor agents. Compound 14o exhibited the strongest inhibitory activity against APN, with IC50 value three orders of magnitude better than that of the positive control bestatin. Furthermore, compound 14o demonstrated potent anti-proliferative activities against tumor cells and anti-angiogenic activity.
Article
Chemistry, Multidisciplinary
Jiaoli Ma, Jing Li, Penghu Guo, Xincheng Liao, Huicheng Cheng
Summary: A series of novel indole derivatives with a-aminophosphonate moieties were synthesized and evaluated for their antitumor activities. Some of these compounds exhibited higher inhibitory activities against cancer cells compared to 5-fluorouracil.
ARABIAN JOURNAL OF CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Siming Yuan, Yang Zhu, Yi Dai, Yu Wang, Duo Jin, Manman Liu, Liqin Tang, Fabio Arnesano, Giovanni Natile, Yangzhong Liu
Summary: Pt-IV prodrugs can overcome resistance and side effects of conventional Pt-II anticancer therapies by efficiently promoting the two electrons reduction of Pt-IV to Pt-II. The activation of Pt-FBA is highly dependent upon the type of cancer cells, and FBA can shuttle out of the cell after Pt-FBA is reduced intracellularly. The F-19 NMR approach has the advantage of avoiding the interference of all background signals when investigating the activation of Pt-IV prodrugs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Inorganic & Nuclear
Nicola Margiotta, Concetta Pacifico, Teresa Saltarella, Giovanni Natile, Francesco P. Intini
Summary: The synthesis and characterization of platinum complexes with the 2-iminotetrahydrofuran ligand, where the iminic nitrogen is outside the cycle and can keep its proton, are described in this paper. Apart from isolating the pure E and Z isomers, diiodido derivative and cis isomer were also prepared.
INORGANICA CHIMICA ACTA
(2022)
Article
Biochemistry & Molecular Biology
Jaroslav Malina, Hana Kostrhunova, Vojtech Novohradsky, Peter Scott, Viktor Brabec
Summary: The design of efficient and safe gene delivery vehicles remains a major challenge for gene therapy. Metal complexes with high affinity for nucleic acids are emerging as an attractive option for gene delivery systems. Certain metallohelices have been discovered to act as nonviral DNA delivery vectors capable of mediating efficient gene transfection, forming globular DNA particles that protect the DNA from degradation, and successfully being processed by cells.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Monika Hreusova, Vojtech Novohradsky, Lenka Markova, Hana Kostrhunova, Ivan Potocnak, Viktor Brabec, Jana Kasparkova
Summary: In this study, a gallium(III) complex with cloxyquin ligands is found to effectively inhibit the proliferation of rhabdomyosarcoma cells, a type of aggressive and difficult-to-treat cancer in children. The complex exhibits selective toxicity towards cancer cells compared to noncancerous fibroblasts. It induces ferroptosis in rhabdomyosarcoma cells through interference with iron metabolism, and is capable of killing both bulk and stem cells. This is the first non-iron metal compound shown to induce ferroptosis in cancer cells.
BIOINORGANIC CHEMISTRY AND APPLICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Alessandra Barbanente, Valentina Gandin, Cecilia Ceresa, Cristina Marzano, Nicoletta Ditaranto, James D. Hoeschele, Giovanni Natile, Fabio Arnesano, Concetta Pacifico, Francesco P. Intini, Nicola Margiotta
Summary: The Pt(IV) prodrug of kiteplatin, cis,trans,cis-[PtCl2(OBz)(2)(cis-1,4-DACH)], has shown promising anticancer activity at nanomolar concentrations, good stability in acidic conditions for oral administration, and comparable tumor reduction effectiveness to cisplatin in in vivo studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Inorganic & Nuclear
Alba Hernandez-Garcia, Lenka Markova, Maria Dolores Santana, Jitka Pracharova, Delia Bautista, Hana Kostrhunova, Vojtech Novohradsky, Viktor Brabec, Jose Ruiz, Jana Kasparkova
Summary: This study presents the synthesis and characterization of six new heteroleptic osmium(II) complexes with varying substituents in the R3 position of the phenyl ring of the cyclometalating C^N ligand. These complexes are highly kinetically inert and absorb a full-wavelength range of visible light. The antiproliferative activity of these complexes has been investigated using human cancer and noncancerous cell cultures, showing that they are more potent than conventional cisplatin. The mechanism of action involves the activation of the endoplasmic reticulum stress pathway and disruption of calcium homeostasis.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Hana Kostrhunova, Brondwyn S. McGhie, Lenka Markova, Olga Novakova, Jana Kasparkova, Janice R. Aldrich-Wright, Viktor Brabec
Summary: The platinum(II) complex Pt(II)56MeSS exhibits high potency against cancer cells but also displays side toxicity and in vivo activity. The synthesis of new platinum(IV) prodrugs combining Pt(II)56MeSS with diclofenac (DCF) is described. These Pt(IV) complexes show similar mechanisms of action as Pt(II)56MeSS and DCF, promoting antiproliferative activity and inducing cell death and immunogenic cell death in cancer cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jaroslav Malina, Hana Kostrhunova, Peter Scott, Viktor Brabec
Summary: Fe(II)-based metallohelices were found to stabilize various DNA junctions, with the highest selectivity for the Y-shaped 3WJ. These metallohelices were shown to efficiently kill cancer cells and induce DNA damage, offering potential therapeutic benefits.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Amrita Sarkar, Vojtech Novohradsky, Moumita Maji, Tomer Babu, Lenka Markova, Hana Kostrhunova, Jana Kasparkova, Valentina Gandin, Viktor Brabec, Dan Gibson
Summary: A multitargeting prodrug (2) that releases gemcitabine, oxaliplatin, and doxorubicin in their active form in cancer cells is a potent cytotoxic agent. It selectively targets cancer cells with high selectivity indices and induces the release of DAMPs in CT26 cells. The prodrug also inhibits tumor growth in murine models with lower body weight loss compared to FDA drugs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Medicinal
Vojtech Novohradsky, Alicia Marco, Lenka Markova, Natalia Cutillas, Jose Ruiz, Viktor Brabec
Summary: In this study, a series of new octahedral iridium(III) complexes Ir1-Ir9 were reported, which showed potential for inhibiting metastasis in triple-negative breast cancer. The results demonstrated that the structural modifications within the complexes strongly influenced their anti-metastatic properties, with complex Ir1 exhibiting the highest activity. Contrary to the effects of the conventional chemotherapy drug doxorubicin, which promoted metastatic properties of TNBC cells, the results suggested that doxorubicin therapy may increase the risk of breast cancer metastasis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
J. P. C. Coverdale, H. Kostrhunova, L. Markova, H. Song, M. Postings, H. E. Bridgewater, V. Brabec, N. J. Rogers, P. Scott
Summary: Self-assembled enantiomers of a di-iron metallohelix showed different antiproliferative activities against HCT116 colon cancer cells, with the ?-helicity compound being more potent than the Delta compound. The accumulation and localization studies suggest that the ? enantiomer undergoes carrier-mediated efflux, while the Delta enantiomer undergoes equilibrative process. The binding of the ? metallohelix to DNA and inhibition of tubulin and actin networks contribute to its G(2)/M arrest effect on cells.
DALTON TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Jitka Pracharova, Hana Kostrhunova, Alessandra Barbanente, Nicola Margiotta, Viktor Brabec
Summary: This study confirms the excellent antiproliferative activity of the phosphaplatin derivative RRD2 in various cancer cell lines and analyzes its binding to nuclear DNA. The results demonstrate that DNA lesions caused by RRD2 contribute to killing cancer cells. Additionally, RRD2 accumulates in cancer cells to a lesser extent than cisplatin but exhibits similar binding efficiency to nuclear DNA after accumulation.
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Jaroslav Malina, Hana Kostrhunova, Viktor Brabec
Summary: In this study, we investigated the interaction between a dinuclear nickel(II) tetracationic supramolecular helicate and DNA G-quadruplexes, and their impact on gene expression. The results showed that the supramolecular helicate preferentially binds to G-quadruplex structures and stabilizes them, leading to the inhibition of DNA synthesis and downregulation of gene expression.
INORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Biochemistry & Molecular Biology
Jana Kasparkova, Hana Kostrhunova, Vojtech Novohradsky, Lili Ma, Guangyu Zhu, Elena R. Milaeva, Alexender A. Shtill, Robin Vinck, Gilles Gasser, Viktor Brabec, Alexey A. Nazarov
Summary: This study investigated the mechanism of action of a Pt(IV) complex 2 with two axial lonidamine ligands, which selectively inhibit aerobic glycolysis. Compared to the parent Pt(II) complex, the presence of two lonidamine ligands increased the antiproliferative activity of complex 2, influenced its cell cycle profile and mechanism of cell death. In 3D cell culture, complex 2 exhibited exceptional antiproliferative activity.
Article
Chemistry, Inorganic & Nuclear
Vojtech Novohradsky, Lenka Markova, Hana Kostrhunova, Marie Svitelova, Jana Kasparkova, Alessandra Barbanente, Paride Papadia, Nicola Margiotta, James D. Hoeschele, Viktor Brabec
Summary: New platinum-based compounds exhibit high potency and selectivity in pancreatic cancer cells, and inhibit lipid synthesis through a novel mechanism, providing a potential theoretical basis for the development of new anticancer drugs.
INORGANIC CHEMISTRY FRONTIERS
(2022)
