Article
Chemistry, Medicinal
Hui Zhong, Mingxuan Zhao, Chunyu Wu, Jiayao Zhang, Li Chen, Jianbo Sun
Summary: A series of oxoisoaporphine derivatives with topoisomerase I inhibition and cytotoxic activities were investigated. Compound 14 exhibited the most potent cytotoxic activity against cancer cell lines and low toxicity to normal cells. Mechanistic studies revealed that 14 could interfere with DNA and inhibit the activity of topoisomerase I, leading to cell cycle arrest and apoptosis. Additionally, 14 showed chemo-reversal ability on multidrug-resistant breast cancer cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Amos O. Akinyemi, George B. S. Pereira, Gabriela P. Oliveira, Mauro A. Lima, Josias S. Rocha, Vinicius A. Costa, Dario B. Fortaleza, Tamara Teixeira, Karine Zanotti, Moacir Rossi Forim, Joao H. Araujo-Neto, Javier Ellena, Fillipe Vieira Rocha
Summary: This research presents the synthesis, characterization, anticancer activity, and investigation of biological targets of three new palladium (II) complexes. The complexes showed significant cytotoxic activity against tumor cells, especially the cisplatin-resistant ovarian tumor cell line. Furthermore, the compounds exhibited potential inhibitory effects on topoisomerase I beta.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Kyung-Hwa Jeon, Seojeong Park, Hae Jin Jang, Soo-Yeon Hwang, Aarajana Shrestha, Eung-Seok Lee, Youngjoo Kwon
Summary: The study revealed that AK-I-190, a novel topoisomerase II inhibitor, exerts potent inhibitory activity by intercalating into DNA without stabilizing the DNA-enzyme cleavage complex, resulting in less DNA toxicity compared to etoposide. AK-I-190 induces G1 arrest and effectively inhibits cell proliferation and colony formation in an androgen receptor-negative CRPC cell line, indicating the potential clinical relevance of topoisomerase II catalytic inhibitors in treating this type of prostate cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Organic
Xuelin Yue, Yijie Gao, Junwei Huang, Yadong Feng, Xiuling Cui
Summary: An efficient method for the synthesis of N substituted indenoisoquinolinones has been developed via rhodium(III)-catalyzed C- H bond activation and subsequent [4 + 2] cyclization. The reaction uses 2-phenyloxazolines and 2-diazo-1,3-indandiones as starting materials and proceeds through C-H functionalization, intramolecular annulation, elimination, and ring opening in one pot under mild conditions, yielding a series of indeno[1,2-c]isoquinolinones with up to 93% yield. This method demonstrates excellent atom-and step-economy and provides a novel strategy for the synthesis of N substituted indenoisoquinolinones and their study of biological activities.
Article
Chemistry, Organic
Xuelin Yue, Yijie Gao, Junwei Huang, Yadong Feng, Xiuling Cui
Summary: An efficient method for synthesizing N substituted indenoisoquinolinones has been developed through rhodium(III)-catalyzed C-H bond activation/subsequent [4 + 2] cyclization. The reaction starts from readily available 2-phenyloxazolines and 2-diazo-1,3-indandiones. This protocol offers excellent atom- and step-economy, providing a novel strategy for the synthesis of N-substituted indenoisoquinolinones and enabling the study of their biological activities.
Article
Multidisciplinary Sciences
Shadi Rabiee, Elham Hoveizi, Mahmood Barati, Ali Salehzadeh, Mohammad Taghi Joghataei, Shima Tavakol
Summary: The cancer microenvironment is crucial in promoting metastasis and malignancy in normal cells. This study investigated the impact of acidic and conditioned media from cancer cells on normal fibroblasts, revealing that acidic media rescued cell survival and altered cell metabolism. The combination of acidic and conditioned media shifted cells towards autophagy rather than apoptosis, and resulted in DNA hypomethylation. Overall, the acidic and conditioned media produced by cancer cells can remotely activate malignant signaling pathways, causing metabolic and epigenetic changes in normal cells.
Article
Biochemistry & Molecular Biology
Keying Zhu, Yang Wang, Heela Sarlus, Keyi Geng, Erik Nutma, Jingxian Sun, Shin-Yu Kung, Cindy Bay, Jinming Han, Jin-Hong Min, Irene Benito-Cuesta, Harald Lund, Sandra Amor, Jun Wang, Xing-Mei Zhang, Claudia Kutter, Andre Ortlieb Guerreiro-Cacais, Bjorn Hogberg, Robert A. Harris
Summary: This study reveals the promise of TOP1 inhibitors for microglial modulation and highlights the therapeutic strategy of TOP1 inhibition in myeloid cells for neuroinflammatory diseases. The designed nanosystem shows enhanced specificity to myeloid cells and prevents the degradation of the DNA scaffold, offering a potential treatment for diseases with dysfunctional myeloid cells.
Article
Infectious Diseases
Pavel A. A. Nazarov, Svetlana A. A. Khrulnova, G. G. Kessenikh, Uliana S. S. Novoyatlova, Svetlana B. B. Kuznetsova, Sergey V. V. Bazhenov, Alexandra I. I. Sorochkina, Marina V. V. Karakozova, Ilya V. V. Manukhov
Summary: The search for new antibiotics is a pressing need in modern medicine. Derivatives of triphenylphosphonium show promise as mitochondria-targeted antioxidants that can protect infected organs and repair damaged cells. Recent studies have shown that these derivatives exhibit antibacterial activity and can inhibit cellular metabolism at submicromolar concentrations. Our findings confirm a decrease in metabolic activity but not a cytocidal effect of triphenylphosphonium derivatives at submicromolar concentrations, suggesting their potential as non-toxic antibacterial drugs and safe vectors for delivering other antibacterial substances into bacterial cells.
Article
Chemistry, Physical
Cansu Gokce Topkaya, Tolga Gokturk, Tuncer Hokelek, Esin Sakalli Cetin, Sultan Kincal, Ramazan Gup
Summary: In this study, a Cu(II) complex containing p-Cl-isonitrosoacetophenone based on N 4-type Schiff base ligand was synthesized and characterized. The complex was found to bind with CT-DNA via intercalation and showed efficient cleavage of supercoiled DNA as well as strong inhibition against topoisomerase enzymes. Additionally, the complex exhibited remarkable cytotoxic potential on certain cancer cell lines.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Oncology
Jeong-Mi Lee, Kwang-Soo Shin, Choong-Hyun Koh, Boyeong Song, Insu Jeon, Myung Hwan Park, Byung-Seok Kim, Yeonseok Chung, Chang-Yuil Kang
Summary: Topoisomerase I inhibitors can alter the immune landscape of tumors and enhance their antitumor effects when combined with immunotherapy. Monocyte-derived dendritic cells (moDCs) induced by these inhibitors can activate antigen-specific CD8+ T cells, contributing to the antitumor response.
Article
Biochemistry & Molecular Biology
Guiying Wu, Hui Zhong, Ying Wang, Li Chen, Jianbo Sun
Summary: A series of NO-releasing quinoline derivatives were designed and synthesized, exhibiting good anti-proliferation activity against cancer cells and drug-resistant cells while showing low toxicity to normal cells. Compound 9, the most potent compound, released high concentration of NO and inhibited the activity of topoisomerase I. It regulated apoptosis-related proteins, generated ROS, and arrested the cell cycle to induce apoptosis. Moreover, compound 9 influenced P-gp-mediated transport and significantly inhibited tumor growth in vivo without observable organ-related toxicities.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Manasa Kadagathur, Sandip Patra, Geetanjali Devabattula, Joel George, Regur Phanindranath, Arbaz Sujat Shaikh, Dilep Kumar Sigalapalli, Chandraiah Godugu, Narayana Nagesh, Neelima D. Tangellamudi, Nagula Shankaraiah
Summary: This study designed and synthesized a series of new small molecular entities for chemotherapy, among which conjugate 11g showed the strongest anti-cancer activity and high selectivity. Further evaluations demonstrated the good cytotoxicity and apoptosis-inducing ability of 11g and 12g. Molecular modeling and toxicity analysis provided further support for the drug-likeness and safety of these compounds. These findings are of great significance for cancer drug development.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Turgut Keles, Burak Barut, Arzu Ozel, Zekeriya Biyiklioglu
Summary: In this study, a series of silicon phthalocyanines and naphthalocyanines compounds were synthesized and characterized, among which SiPc1a showed the highest cytotoxicity. Cell cycle analysis indicated that it could inhibit cell proliferation by arresting cells in the G(0)/G(1) phase.
BIOORGANIC CHEMISTRY
(2021)
Article
Gastroenterology & Hepatology
Chiao-Ling Tsai, Po-Sheng Yang, Feng-Ming Hsu, Ann-Lii Cheng, Wan-Ni Yu, Jason Chia-Hsien Cheng
Summary: This study investigated the effect of TOP1 inhibition and DNA-PKcs/RNF144A mechanism on radiosensitization mediated by natural killer (NK) cells in radiation therapy (RT). The results showed that TOP1 inhibitors and RT had a synergistic effect on hepatocellular carcinoma (HCC) cells, enhancing the anti-HCC effect of RT through increased DNA damage and DNA-PKcs signaling. RNF144A mediated DNA-PKcs ubiquitination and provided a reason for the difference in radiosensitization effect between HCC cells.
JOURNAL OF CLINICAL AND TRANSLATIONAL HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kiyohiro Ando, Yusuke Suenaga, Takehiko Kamijo
Summary: Identifying the vulnerability of altered DNA repair machinery that displays synthetic lethality with MYCN amplification is a therapeutic rationale in unfavourable neuroblastoma. However, none of the inhibitors for DNA repair proteins are established as standard therapy in neuroblastoma. DNA-PK inhibitor (DNA-PKi) showed inhibitory effects on the proliferation of MYCN-driven neuroblastoma spheroids and cell lines. Among them, DNA ligase 4 (LIG4) was identified as a prognostic factor and its inhibition combined with DNA-PKi may overcome resistance to multimodal therapy in MYCN-amplified neuroblastoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Andrology
Mehlika Ercan, Hamit Hakan Alp, Huseyin Kocaturk, Nuri Bakan, Mustafa Gul
Article
Chemistry, Organic
Mehtap Tugrak, Halise Inci Gul, Hiroshi Sakagami, Ilhami Gulcin
JOURNAL OF HETEROCYCLIC CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Mehtap Tugrak, Halise Inci Gul, Yeliz Demir, Ilhami Gulcin
Summary: A series of novel compounds with potential and selective inhibitory effects on human carbonic anhydrase I and II were synthesized, demonstrating promise as candidate drugs for treating glaucoma. Some compounds showed significant inhibitory effects against the target proteins, highlighting their potential for further investigation as lead compounds in alleviating glaucoma symptoms.
ARCHIV DER PHARMAZIE
(2021)
Article
Chemistry, Medicinal
Mehtap Tugrak, Halise Inci Gul, Yeliz Demir, Serkan Levent, Ilhami Gulcin
Summary: New imidazolinone-based benzenesulfonamides were synthesized and evaluated for their potential as drug candidates by testing their activities against carbonic anhydrase (CA) and acetylcholinesterase (AChE) enzymes. Compounds with nitro group showed increased selectivity in CA inhibition compared to their hydrogen counterparts, while compounds with sulfanilamide moiety exhibited the best AChE inhibitory potency.
ARCHIV DER PHARMAZIE
(2021)
Review
Chemistry, Medicinal
Serap Sahin-Bolukbasi, Pakize Canturk-Kilickaya, Ozan Kilickaya
Summary: The pharmaceutical industry is using computational tools more frequently to screen drug candidates, with N-heterocyclic carbenes (NHCs) being evaluated as potential candidates due to their anti-cancer and anti-inflammatory properties. Recent studies have focused on Ag(I)-NHC complexes and their anti-cancer activities, as well as the utilization of density functional theory and structure-activity relationship in drug development.
DRUG DEVELOPMENT RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Reem Aljanabi, Lina Alsous, Dima A. Sabbah, Halise Inci Gul, Mustafa Gul, Sanaa K. Bardaweel
Summary: Monoamine oxidases (MAOs) are oxidative enzymes responsible for converting biogenic amines into aldehydes and ketones. Distorted activity of MAOs has been linked to neurological diseases, and recent studies have found unexpected roles of MAOs in tumor progression and metastasis. Chemical inhibition of MAOs may be a valuable therapeutic approach for cancer treatment.
Article
Chemistry, Medicinal
Betul Cicek, Ahmet Hacimuftuoglu, Mehmet Kuzucu, Ahmet Cetin, Yesim Yeni, Sidika Genc, Serkan Yildirim, Ismail Bolat, Mecit Kantarci, Mustafa Gul, Serhat Hayme, Dimitris Matthaios, Dimitra P. P. Vageli, Sotirios G. G. Doukas, Aristidis Tsatsakis, Ali Taghizadehghalehjoughi
Summary: According to population-based studies, lung cancer is the most common cause of cancer-related deaths worldwide in males, and its incidence among females is also increasing alarmingly. Sorafenib (SOR), a multitargeted protein kinase inhibitor used for the treatment of hepatocellular carcinoma and renal cell carcinoma, has been the subject of interest in preclinical and clinical trials for lung cancer. This study aimed to investigate the effects of SOR in diethylnitrosamine (DEN)-induced lung carcinogenesis and explore its mechanisms of action. The results showed that SOR reduced the levels of SOX-2, TNF-alpha, and IL-1 beta, and alleviated the histopathological damage caused by DEN-induced lung carcinogenesis. Immunohistochemical and immunofluorescence analysis also revealed that SOR treatment decreased the expression of COX-2 and JNK in DEN-intoxicated rats. These findings suggest that SOR inhibits lung precancerous lesions induced by DEN through reducing inflammation and SOX-2 levels.
Article
Medicine, Research & Experimental
Hilal Ustundag, Esra Senturk, Serkan Yildirim, Fikret celebi, Mustafa Gul
Summary: The objective of this study was to investigate the effects of in vivo melatonin administration on thoracic aorta in thyroxine-treated rats and its role in the aortic response to contractile agents. The results demonstrated that melatonin partially attenuated the reduction in contraction responses caused by thyroxine treatment. Immunohistological findings indicated that melatonin inhibited vessel wall thickening by suppressing collagen formation.
CLINICAL AND EXPERIMENTAL HEALTH SCIENCES
(2023)
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
Biochemistry & Molecular Biology
Ege Gok, Naz Unal, Burcin Gungor, Gulderen Karakus, Savas Kaya, Pakize Canturk, Konstantin P. Katin
Summary: Cancer is a disease caused by abnormal or uncontrolled growth of cells due to DNA damage. This study evaluated the anticancer effects of Istaroxime, a compound that inhibits Sarco-endoplasmic reticulum Ca2+ATPase (SERCA2a). The results showed that Istaroxime exhibited an antiproliferative effect on cancer cell lines and inhibited Topoisomerase I, indicating its potential as a Topoisomerase I inhibitor. Molecular docking analysis and chemical reactivity computations further supported these findings.
Article
Chemistry, Multidisciplinary
Mehtap Tugrak, Halise Inci Gul, Hiroshi Sakagami, Ruya Kaya, Ilhami Gulcin
Summary: Cancer is characterized by uncontrolled cell growth, and developing new drug candidate compounds is necessary due to limitations and side effects of existing drugs. In this study, new pyrazole-sulphonamide hybrid compounds were designed and synthesized, with compounds 4i and 4g showing the highest cytotoxicity values. These compounds have the potential to be lead compounds for further research.
TURKISH JOURNAL OF CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Mehtap Tugrak, Halise Inci Gul, Baris Anil, Ilhami Gulcin
TURKISH JOURNAL OF CHEMISTRY
(2020)
Meeting Abstract
Physiology
Betul Cicek, Esra Senturk, Mustafa Gul, Fikret Celebi, Hilal Ustundag, Murat Senturk
Meeting Abstract
Physiology
Hilal Ustundag, Mustafa Gul