Article
Biochemistry & Molecular Biology
Hadeer K. Swedan, Asmaa E. Kassab, Ehab M. Gedawy, Salwa E. Elmeligie
Summary: DNA topoisomerase enzymes are essential for cell function and have been targeted by antibacterial and cancer chemotherapeutic drugs. This review focuses on the recent advances in the anti-cancer activity of topoisomerase II inhibitors (anthracyclines, epipodophyllotoxins, and fluoroquinolones), their modes of action, and structure-activity relationships (SARs). The review also highlights promising new topoisomerase II inhibitors and their mechanism of action and SARs.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Ivina P. de Souza, Ariane C. C. de Melo, Bernardo L. Rodrigues, Adailton Bortoluzzi, Simon Poole, Zara Molphy, Vickie McKee, Andrew Kellett, Rodrigo B. Fazzi, Ana M. da Costa Ferreira, Elene C. Pereira-Maia
Summary: Five ternary copper(II) complexes were synthesized and characterized. Two complexes showed strong anti-cancer activity and DNA cleavage ability.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Sourav Acharya, Moumita Maji, Manas Pratim Chakraborty, Indira Bhattacharya, Rahul Das, Arnab Gupta, Arindam Mukherjee
Summary: Platinum-based and Ruthenium-based complexes have been investigated as potential chemotherapeutic agents with tunable activity against platinum-resistant cancer cells. N,O-coordinated platinum complexes showed superior in vitro antiproliferative activity compared to N,N-coordinated ruthenium complexes, especially against aggressive cancer cells. The complexes also demonstrated disruption of the microtubule network, cell cycle arrest, and apoptotic cell death, indicating their potential for cancer treatment. Among the studied complexes, the platinum-based complexes exhibited higher cytotoxicity, better VEGFR2 inhibition, and strong interaction with a model nucleobase.
INORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Durgesh Gurukkala Valapil, Priyanka Mishra, Kalyani Jungare, Nagula Shankaraiah
Summary: A facile [3+3] annulation method for the construction of fused a-carboline or indolo[2,3-c]isoquinoline frameworks from easily synthesizable N,N'-cyclic azomethine ylides and 3-diazoindolin-2-imines using a Ru(II) catalyst is reported. This strategy was found to be efficient and effective for the syntheses of a variety of fused polycyclic molecules with a wide substrate scope, mild reaction conditions, and good to excellent yields. In addition, the mechanistic pathway of this transformation has been investigated by performing various control experiments with ESI-MS analyses.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mohammed Farrag El-Behairy, Walaa Hamada Abd-Allah, Mohamed M. M. Khalifa, Mohamed S. S. Nafie, Mohamed A. A. Saleh, Mohammed S. S. Abdel-Maksoud, Tarfah Al-Warhi, Wagdy M. M. Eldehna, Ahmed A. A. Al-Karmalawy
Summary: Based on the rigidification principle and doxorubicin's pharmacophoric features, two novel series of dibenzo[b,f]azepines (14 candidates) were designed and synthesised. The anti-proliferative activity and topoisomerase II inhibition ability of the promising candidates (5a-g) were evaluated, with 5e identified as the most active congener. Moreover, 5e exhibited cytotoxicity against leukaemia SR cells, arrested the cell cycle at the G1 phase, increased apoptosis ratio, and showed inhibition of tumor proliferation and volume decrease in in vivo studies.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ziga Skok, Martina Durcik, Ziva Zajex, Darja Gramec Skledar, Kristof Bozovic, Anja Pis, Tihomir Tomas, Anamarija Zega, Lucija Peterlin Mas, Danijel Kikelj, Nace Zidar, Janez Ilas
Summary: Based on recent screening hits, we developed and evaluated a series of new and improved N-phenylpyrrolamide DNA topoisomerase II inhibitors. These compounds show potential in becoming successors to topoisomerase II poisons, as they exhibit high inhibitory activity and metabolic stability.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Carolyn N. Krasner, Susana M. Campos, Chantay L. Young, Karan R. Chadda, Hang Lee, Michael J. Birrer, Neil S. Horowitz, Panagiotis A. Konstantinopoulos, Antonella M. D'Ascanio, Ursula A. Matulonis, Richard T. Penson
Summary: CRLX101, as a novel cyclodextrin-containing polymer conjugate of camptothecin, shows promising efficacy in treating recurrent epithelial ovarian cancer, with good tolerability. When combined with bevacizumab, it can improve clinical benefit rates and overall response rates without severe adverse events.
GYNECOLOGIC ONCOLOGY
(2021)
Article
Chemistry, Inorganic & Nuclear
Patryk Borowski, Sylwia E. Kutniewska, Radoslaw Kaminski, Adam Krowczynski, Dominik Schaniel, Katarzyna N. Jarzembska
Summary: Two photoswitchable nickel and copper coordination compounds were studied, and their structural and switchable properties were compared. The copper complexes showed moderate conversion to a metastable linkage isomer under specific light irradiation, while the nickel complexes transformed into theendo-nitritoforms. The isomerization reaction was proven to be fully reversible.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Zhongpeng Ding, Feifei Li, Lianghui Xie, Minqing Gu, Chunlei Li, Chang Liu, Chao Peng, Wenbao Li
Summary: In this study, novel phenylahistin derivatives were designed and synthesized, and it was found that appropriate hydrocarbon and unsaturated alkenyl substituents are important for enhancing their activity. Compound 15p showed potent cytotoxic activity against human lung cancer cells at the nanomolar level, inhibited microtubule polymerization, and induced high expression of caspase-3. In vivo experiments demonstrated that compound 15p effectively inhibited the growth of H22 transplanted tumors with lower toxicity compared to standard drugs. These findings suggest that the novel phenylahistin derivatives could be safe and effective potential agents for cancer treatment.
Article
Chemistry, Physical
Andrea Pastrana-Davila, Andres Amaya-Florez, Carlos Aranaga, Javier Ellena, Mario Macias, Edwin Florez-Lopez, Richard F. D'Vries
Summary: In this study, dibenzylamine derivatives were synthesized through two methodologies and used to obtain dithiocarbamate ligands and coordination compounds. The compounds were extensively characterized using various spectroscopic and thermal techniques, and microbial inhibition tests were conducted with promising results.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Biochemistry & Molecular Biology
Aarajana Shrestha, Soo-Yeon Hwang, Surendra Kunwar, Tara Man Kadayat, Seojeong Park, Yi Liu, Hyunji Jo, Naeun Sheen, Minjung Seo, Eung-Seok Lee, Youngjoo Kwon
Summary: Topoisomerases are important enzymes for altering DNA topology and have been considered as attractive targets for chemotherapeutic agents. In this study, we presented new di-indenopyridine compounds with inhibitory activity against topoisomerase I/II and alpha. Compound 17 showed 100% inhibition of topoisomerase II and alpha at 20 μM concentration, as well as comparable antiproliferative activity against tested cell lines. These findings highlight the significance of specific groups at the 4-position of the indane ring in designing potent catalytic topoisomerase II and alpha inhibitors with anticancer effects.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Maria Kashina, Konstantin Luzyanin, Eugene A. Katlenok, Alexander S. Novikov, Mikhail A. Kinzhalov
Summary: In this study, platinum and palladium complexes were synthesized through metal-mediated coupling reactions, and thiocyanate complexes were prepared through ligand exchange reactions. The characterization and evaluation of these compounds were performed, and the electronic structure and bonding nature were studied through X-ray diffraction and theoretical considerations. Additionally, it was demonstrated that two of the thiocyanate derivatives formed supramolecular dimers with symmetrical pairs. Furthermore, some of the compounds were evaluated as photocatalysts.
DALTON TRANSACTIONS
(2022)
Article
Biochemistry & Molecular Biology
Endri Karaj, Samkeliso Dlamini, Radhika Koranne, Shaimaa H. Sindi, Lalith Perera, William R. Taylor, L. M. Viranga Tillekeratne
Summary: This study reports a new class of imidazole-based chalcones as potential antimitotic agents and investigates their structure-activity relationship. The second-generation analogs in this class show superior bioactivity and exhibit a privileged pharmacological pharmacophore of chalcones. These compounds have unique mechanisms of cytotoxic activity.
BIOORGANIC CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Afif F. Bandak, Tim R. Blower, Karin C. Nitiss, Raveena Gupta, Albert Y. Lau, Ria Guha, John L. Nitiss, James M. Berger
Summary: Type II topoisomerases temporarily cleave duplex DNA to control chromosomal organization, and mutations in hTOP2(3) can make the enzyme hypersensitive to the drug etoposide, leading to cell death. Some of these mutations are also found in cancer genome databases. These findings suggest a link between DNA cleavage predisposition and sensitivity to topoisomerase II poisons in cancer cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Chemistry, Medicinal
Tanuja T. Yadav, Manikanta Murahari, G. J. Peters, Y. C. Mayur
Summary: The clinical efficacy of existing anticancer drugs has been reduced due to drug resistance and severe side-effects. Therefore, the development of new anti-cancer drugs with minimal adverse effects is always needed. Acridone is a promising heterocycle that has gained attention for its ability to act on various molecular targets, overcome drug resistance, and intercalate DNA in cancer cells. Some acridone derivatives have already entered clinical studies and have shown great potential in cancer therapeutics and imaging.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)