Discovery of steroidal lactam conjugates of POPAM-NH2 with potent anticancer activity

2020 ◽  
Vol 12 (1) ◽  
pp. 19-35 ◽  
Author(s):  
Dimitrios Trafalis ◽  
Panagiotis Dalezis ◽  
Elena Geromichalou ◽  
Sofia Sagredou ◽  
Eleni Sflakidou ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Alkylating Agents ◽  
Experimental Models ◽  
The Novel ◽  
Nitrogen Mustards ◽  
Experimental Systems ◽  
High Antitumor Activity

Aim: Steroidal prodrugs of nitrogen mustards such as estramustine and prednimustine have proven effective anticancer agents in clinical use since the 1970s. In this work, we aimed to develop steroidal prodrugs of the novel nitrogen mustard POPAM-NH2. POPAM-NH2 is a melphalan analogue that was coupled with three different steroidal lactams. Methodology: The new conjugates were preclinically tested for anticancer activity against nine human and one rodent cancer experimental models, in vitro and in vivo. Results & conclusion: All the steroidal alkylators showed high antitumor activity, in vitro and in vivo, in the experimental systems tested. Moreover, these hybrid compounds showed by far superior anticancer activity compared with the alkylating agents, melphalan and POPAM-NH2.

Alkaloids as Anticancer Agents: A Review of Chinese Patents in Recent 5 Years

2020 ◽  
Vol 15 (1) ◽  
pp. 2-13 ◽  
Author(s):  
Hongyu Tao ◽  
Ling Zuo ◽  
Huanli Xu ◽  
Cong Li ◽  
Gan Qiao ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Cdk Inhibitors ◽  
Comprehensive Overview ◽  
P53 Expression ◽  
Study Results

Background: In recent years, many novel alkaloids with anticancer activity have been found in China, and some of them are promising for developing as anticancer agents. Objective: This review aims to provide a comprehensive overview of the information about alkaloid anticancer agents disclosed in Chinese patents, and discusses their potential to be developed as anticancer drugs used clinically. Methods: Anticancer alkaloids disclosed in Chinese patents in recent 5 years were presented according to their mode of actions. Their study results published on PubMed, and SciDirect databases were presented. Results: More than one hundred anticancer alkaloids were disclosed in Chinese patents and their mode of action referred to arresting cell cycle, inhibiting protein kinases, affecting DNA synthesis and p53 expression, etc. Conclusion: Many newly found alkaloids displayed potent anticancer activity both in vitro and in vivo, and some of the anticancer alkaloids acted as protein kinase inhibitors or CDK inhibitors possess the potential for developing as novel anticancer agents.

Recent Development of 1,2,4-triazole-containing Compounds as Anticancer Agents

2020 ◽  
Vol 20 (16) ◽  
pp. 1441-1460 ◽  
Author(s):  
Xiaoyue Wen ◽  
Yongqin Zhou ◽  
Junhao Zeng ◽  
Xinyue Liu
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Mechanisms Of Action ◽  
Triazole Derivatives ◽  
Recent Advances

1,2,4-Triazole derivatives possess promising in vitro and in vivo anticancer activity, and many anticancer agents such as fluconazole, tebuconazole, triadimefon, and ribavirin bear a 1,2,4-triazole moiety, revealing their potential in the development of novel anticancer agents. This review emphasizes the recent advances in 1,2,4-triazole-containing compounds with anticancer potential, and the structureactivity relationships as well as mechanisms of action are also discussed.

Synthesis and In Vitro Anticancer Activity of 6-Ferrocenylpyrimidin-4(3H)-one Derivatives

2019 ◽  
Vol 16 (1) ◽  
pp. 160-164 ◽  
Author(s):  
Stanislav A. Grabovskiy ◽  
Rinat S. Muhammadiev ◽  
Lenar R. Valiullin ◽  
Ivan S. Raginov ◽  
Natalie N. Kabal'nova
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Practical Interest ◽  
Breast Adenocarcinoma ◽  
Human Skin Fibroblast ◽  
Normal Human Skin ◽  
Normal Human ◽  
Mcf 7

Aim and Objective: Some ferrocenyl derivatives are active in vitro and in vivo against cancer. Generally, ferrocenyl derivatives for cancer research have three key components: a ferrocene moiety, a conjugated linker that lowers the oxidation potential and some derivative (peptide, nucleobase and others) that can interact with biomolecules. Since the pyrimidine fragment can easily pass through the membrane into the cells and become involved in metabolism; it appears to be promising. Furthermore, this fragment is an electron-acceptor group, so a spacer can be excluded. Therefore, the synthesis of 6-ferrocenylpyrimidin-4(3H)-one derivatives and the study of their anticancer activity have scientific and practical interest. </P><P> Methods: The syntheses of 6-ferrocenylpyrimidin-4(3H)-one derivatives were performed by the condensation of ethyl 3-ferrocenyl-3-oxopropionate with thiourea or acetamidine or guanidine. The cytotoxicity of four 6- ferrocenylpyrimidin-4(3H)-one derivatives was evaluated by using the MTT assay in vitro against Human breast adenocarcinoma MCF-7 and normal human skin fibroblast HSF cells. The tested derivatives induced a concentration-dependent cytotoxic response in cell lines. </P><P> Results: A study of the cytotoxic activity of 6-ferrocenylpyrimidin-4(3H)-one derivatives by the MTT test has found that all compounds have a dose-dependent toxic effect on the lines of breast cancer cells (MCF-7) and normal human fibroblast cells (HSF). The most pronounced cytotoxic effect is exhibited by 2-methyl-6-ferrocenylpyrimidin- 4(3H)-one (MCF-7, IC50 17 ± 1 µM). Conclusion: The experimental results confirm the importance of investigation and design of ferrocenylpyrimidin- 4(3H)-one derivatives as anticancer agents. Compounds where the pyrimidine derivatives are directly linked to the ferrocene unit rather than via a spacer group also may be of interest for antiproliferative drug design.

Ru(III) complexes of pyrazolopyrimidines as anticancer agents: In vitro, in vivo anticancer activity and underlying multi-mechanisms

2022 ◽  
Author(s):  
Yunqiong Gu ◽  
Wen-Ying Shen ◽  
Qi-Yuan Yang ◽  
Zhen-Feng Chen ◽  
Hong Liang
Keyword(s):  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Human Liver ◽  
Normal Human Liver ◽  
Normal Human ◽  
Low Toxicity

Three ruthenium(III) complexes with pyrazolopyrimidine [Ru(Ln)(H2O)Cl3] (13, n=13) were prepared and characterized. These Ru(III) compounds show strong cytotoxicity against six cancer cell lines and low toxicity to normal human liver...

scholarly journals Synergy between Auranofin and Celecoxib against Colon Cancer In Vitro and In Vivo through a Novel Redox-Mediated Mechanism

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 931 ◽  
Author(s):  
Yi Han ◽  
Ping Chen ◽  
Yanyu Zhang ◽  
Wenhua Lu ◽  
Wenwen Ding ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Anticancer Activity ◽  
High Throughput Screening ◽  
Redox Homeostasis ◽  
Single Agent ◽  
Experimental Models ◽  
Clinical Applications ◽  
Moderate Activity

Recent study suggests that auranofin (AF), a US Food and Drug Administration (FDA)-approved drug for treatment of rheumatoid arthritis, has selective anticancer activity in various experimental models. Its clinical applications in cancer treatment, however, have been hampered due in part to its relatively moderate activity as a single agent. In this study, we performed a high-throughput screening of the FDA-approved drug library for clinical compounds that potentiate the anticancer activity auranofin, and unexpectedly identified an anti-inflammatory drug celecoxib (CE) that potently enhanced the therapeutic activity of AF in vitro and in vivo. Mechanistically, AF/CE combination induced severe oxidative stress that caused ROS-mediated inhibition of hexokinase (HK) and a disturbance of mitochondrial redox homeostasis, resulting in a significant decrease of ATP generation. The CE-induced ROS increase together with AF-medicated inhibition of thioredoxin reductase cause a shift of Trx2 to an oxidized state, leading to degradation of MTCO2 and dysfunction of the electron transport chain. Our study has identified a novel drug combination that effectively eliminates cancer cells in vivo. Since AF and CE are FDA-approved drugs that are currently used in the clinic, it is feasible to translate the findings of this study into clinical applications for cancer treatment.

scholarly journals Cholecystokinin-1 receptor antagonists: 5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents

MedChemComm ◽  
2016 ◽  
Vol 7 (6) ◽  
pp. 1138-1145 ◽  
Author(s):  
E. Lattmann ◽  
S. T. Russell ◽  
C. H. Schwalbe ◽  
A. Shortt ◽  
P. N. Balaram ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Anticancer Activity ◽  
Anticancer Agents ◽  
Receptor Antagonists

Hydroxy-pyrrolones, which were potent CCK1R antagonists, showed nanomolar in vitro activity and anticancer activity in vivo for colon and pancreatic cancer.

Design and in vitro biological evaluation of substituted chalcones synthesized from nitrogen mustards as potent microtubule targeted anticancer agents

2017 ◽  
Vol 41 (10) ◽  
pp. 4096-4109 ◽  
Author(s):  
X. Janet Sabina ◽  
J. Karthikeyan ◽  
Gunasekaran Velmurugan ◽  
M. Muthu Tamizh ◽  
A. Nityananda Shetty
Keyword(s):  
Single Crystal ◽  
Anticancer Activity ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
X Ray Diffraction ◽  
Nitrogen Mustards ◽  
X Ray

Six chalcones were synthesized and their structures determined by single crystal X-ray diffraction studies. They exhibited enhanced anticancer activity and tubulin inhibition.

1,3,5-Triazine-azole Hybrids and their Anticancer Activity

2020 ◽  
Vol 20 (16) ◽  
pp. 1481-1492
Author(s):  
Hua Guo ◽  
Quan-Ping Diao
Keyword(s):  
Clinical Trials ◽  
Anticancer Activity ◽  
Anticancer Agents ◽  
Mechanisms Of Action ◽  
Structure Activity ◽  
Hybrid Molecules ◽  
Excellent Activity ◽  
Enhance Efficiency

1,3,5-Triazine and azole can interact with various therapeutic targets, and their derivatives possess promising in vitro and in vivo anticancer activity. Hybrid molecules have the potential to enhance efficiency, overcome drug resistance and reduce side effects, and many hybrid molecules are under different phases of clinical trials, so hybridization of 1,3,5-triazine with azole may provide valuable therapeutic intervention for the treatment of cancer. Substantial efforts have been made to develop azole-containing 1,3,5-triazine hybrids as novel anticancer agents, and some of them exhibited excellent activity. This review emphasizes azole-containing 1,3,5-triazine hybrids with potential anticancer activity, and the structure-activity relationships as well as the mechanisms of action are also discussed to provide comprehensive and target-oriented information for the development of this kind of anticancer drugs.

scholarly journals Investigation of the in vitro Anticancer Activity of Sorbus aria Extract on Prostate Cancer

2020 ◽  
Vol 3 (1) ◽  
pp. 228-235
Author(s):  
Tilbe Özar ◽  
M. Fatih Özalp ◽  
Erdal Eroğlu
Keyword(s):  
Prostate Cancer ◽  
Anticancer Activity ◽  
Anticancer Agents ◽  
Ethanol Extract ◽  
Central Anatolia ◽  
In Vivo Studies ◽  
Total Phenol Content ◽  
Sorbus Aria

Cancer is one of the common diseases observed in our country and worldwide with a high mortality rate. Although cancer has been treated with different applications such as chemotherapy, radiotherapy and surgical operation, the exact remedy of this disease has still not been found, yet. The fact that current treatment methods have severe side effects on patients has increased the interest in natural anticancer agents that are accepted easily and considered as safer by society. The aim of this study is to investigate the anticancer activity of whitebeam (Sorbus aria) that grows in the Central Anatolia Region in Turkey, extract on PC-3 human prostate cancer cells in vitro. The anticancer activity of the ethanol extract obtained from whitebeam fruits evaluated using MTT cell proliferation assay. Also, Folin-Ciocalteu assay and CUPRAC method were performed to determine total phenol content and antioxidant capacity of whitebeam fruits, respectively. Whitebeam fruit extract showed strong anticancer activity on prostate cancer in vitro. The obtained ethanol extract is found to be a promising natural anticancer agent in vitro, and our findings need to be verified with in vivo studies and clinical trials.

scholarly journals The therapeutic potential of the novel ribonuclease ranpirnase (Onconase®) in the treatment of malignant mesothelioma

2011 ◽  
pp. 61-65
Author(s):  
Luciano Mutti ◽  
Giovanni Gaudino
Keyword(s):  
Malignant Mesothelioma ◽  
Anticancer Agents ◽  
Therapeutic Potential ◽  
Phase Iii ◽  
The Novel ◽  
Phase Iii Study ◽  
Large Phase ◽  
Tumor Types

Ribonucleases are a superfamily of RNA-cleaving enzymes that can be cytotoxic since the cleavage of RNA makes its information indecipherable. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA, thus leading to an inhibition of protein synthesis and, ultimately, to cytostasis and cytotoxicity. Ranpirnase has demonstrated antitumor activity both in vitro and in vivo in several tumor models, including malignant mesothelioma. A large phase II trial showed that ranpirnase has diseasemodifying activity against mesothelioma. A first phase III study demonstrated that rampirnase may be combined with doxorubicin and that such an association is more active than Ranpirnase alone against mesothelioma. At present, another large, phase III trial in combination with doxorubicin has completed enrollment and its results are awaited. In all the above studies, ranpirnase died not demonstrate conventional anticancer activity, stabilizing progressive disease and potentially prolonging patients’ survival. Finally, a better understanding of its mechanism of action, coupled with its favorable toxicity profile, especially characterized by the lack of major hematologic toxicities, makes ranpirnase an attractive drug to test in combination with other anticancer agents, in MMe as well as in other tumor types.

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