Recent developments in the synthesis and anti-cancer activity of acridine and xanthine-based molecules

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Sasadhar Majhi

Abstract Cancer is the uncontrolled growth and development of abnormal cells which is a major cause of death in both advanced and emerging countries. Although currently chemotherapy is most broadly used among an extensive range of anti-cancer therapies, it includes many demerits, such as highly toxic, side-effects, expensive and partial lack of targeting specificity. So the design and synthesis of new molecules that perform specifically on target proteins in tumor cells is a focus of contemporary research. So many researchers aim for new drugs that will be more efficient, more selective, and less toxic. Because of the interesting structures and significant biological profile, naturally occurring acridines and xanthines as well as their analogues have attracted considerable interest in researchers and technologists. Natural and synthetic acridine derivatives form a significant category of heterocycles having nitrogen that is of considerable interest for organic chemists and biological communities due to their attractive anti-cancer activity. Another important class of therapeutic agents with diverse biological properties including cytotoxic effects is xanthine derivatives which are collectively called xanthines (a group of alkaloids). Among many significant molecules based on the structure of the purine, there is a group of natural xanthines, involving theobromine, caffeine, and theophylline and analogues of xanthine display anti-cancer activity. Hence the present chapter wishes to concentrate the attention on the synthesis and anti-cancer activity of acridine and xanthine-based compounds brilliantly.

2014 ◽  
pp. 98-101
Author(s):  
Thi Bich Hien Le ◽  
Viet Duc Ho ◽  
Thi Hoai Nguyen

Nowadays, cancer treatment has been a big challenge to healthcare systems. Most of clinical anti-cancer therapies are toxic and cause adverse effects to human body. Therefore, current trend in science is seeking and screening of natural compounds which possess antineoplastic activities to utilize in treatment. Uvaria L. - Annonaceae includes approximately 175 species spreading over tropical areas of Asia, Australia, Africa and America. Studies on chemical compositions and pharmacological effects of Uvaria showed that several compound classes in this genus such as alkaloid, flavonoid, cyclohexen derivaties, acetogenin, steroid, terpenoid, etc. indicate considerable biological activities, for example anti-tumor, anti-cancer, antibacterial, antifungal, antioxidant, etc. Specifically, anti-cancer activity of fractions of extract and pure isolated compounds stands out for cytotoxicity against many cancer cell lines. This study provides an overview of anti-cancer activity of Uvaria and suggests a potential for further studies on seeking and developing novel anti-cancer compounds. Key words: Anti-cancer, Uvaria.


2021 ◽  
Vol 25 (11) ◽  
pp. 104-109
Author(s):  
Gullapelli Kumaraswamy ◽  
Ravichandar Maroju ◽  
Srinivas Bandari ◽  
Gouthami Dasari ◽  
Gullapelli Sadanandam

A novel series of 2-(1-((1-substitutedphenyl-1H-1,2,3- triazol-4-yl)methoxy)ethyl)-1-((1-substituted phenyl- 1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazole (3a-j)derivatives was synthesized in moderate to high yields. The structures of all the synthesized compounds were characterized by 1HNMR, 13CNMR and Mass spectroscopic methods. The title compounds were screened for their anti-oxidant activity and anti-cancer activity. The cancer activity results reveal that the compounds 3j, 3b and 3f are showing promising activity and remaining compounds exhibited moderate activity against all the tested cancer cell lines. The anti-oxidant activity also shows that the compounds 3c and 3d have shown excellent activity and remaining compounds were also found to exhibit moderate activity against the test organisms employed.


2018 ◽  
Vol 143 ◽  
pp. 1968-1980 ◽  
Author(s):  
Junjie Lan ◽  
Lan Huang ◽  
Huayong Lou ◽  
Chao Chen ◽  
Tangjingjun Liu ◽  
...  

2021 ◽  
Author(s):  
Natalie Carroll ◽  
Alena Smith ◽  
Brian A. Salvatore ◽  
Elahe Mahdavian

Abstract Background: Fusarochromanone (FC101) is a small molecule with potent anti-cancer activity. It was originally derived from the fungal plant pathogen, Fusarium equiseti, and it has also been synthesized in non-racemic form in our lab. Numerous studies reveal the promising biological activity of FC101, including potent anti-angiogenic and anti-cancer activity. While FC101 is potent as a single drug treatment across many cancer cell lines, current cancer therapies often incorporate a combination of drugs in order to increase efficacy and decrease the development of drug resistance. In this study, we leverage drug combinations and cellular phenotypic screens to address important questions about FC101’s mode of action and its potential synergies as an anti-cancer therapeutic agent in triple negative breast cancer (TNBC).Method: We hypothesized that FC101’s activity against TNBC is similar to the known mTOR inhibitor, everolimus, because FC101 reduces the phosphorylation of two key mTOR substrates, S6K and S6. Since everolimus synergistically enhances the anti-cancer activities of known EGFR inhibitors (erlotinib or lapatinib) in TNBC, we performed analogous studies with FC101. Phenotypic cellular assays helped assess whether FC101 (in both single and combination treatments) acts similarly to everolimus.Results: FC101 outperformed all other single treatments in both cell proliferation and viability assays. Unlike everolimus, however, FC101 brought about a sustained decrease in cell viability in drug washout studies. None of the other drugs were able to maintain comparable effects upon removal of the treatment agents. Although we observed slightly additive effects when the TNBC cells were treated with FC101 and either EGFR inhibitor, those effects were not truly synergistic in the manner displayed with everolimus. Conclusion: Our results rule out direct inhibition of mTOR by FC101 and suggest that FC101 acts through a different mechanism than everolimus. This lays the foundation for the refinement of our hypothesis in order to better understand FC101’s mode of action as a novel anti-cancer agent.


2019 ◽  
Vol 6 ◽  
pp. 21-32
Author(s):  
Ewelina Piktel ◽  
Robert Bucki

Constantly increasing morbidity and mortality of cancer, complex immunopathogenesis of tumors and variable development and severity of the disease, enforce a constant search for new therapeutic factors with anti-cancer activity. Despite the constant achievements in anti- -cancer diagnostic and therapeutic methods development, the low specificity and high toxicity of cytostatics, and the multidrug resistance expansion, still remain a considerable health problem. Currently, natural, cationic antimicrobial peptides (AMPs) and their synthetic lipid analogs from the ceragenin group (CSA) are presented as potential antineoplastic compounds. Their special features, including the membrane permeabilizing-based mechanism of action, selectivity towards tumor cells, biocompatibility and the absence of a recorded anti-AMPs resistance mechanism, make cationic antineoplastic peptides an effective alternative to modern cytostatics. Moreover, a compelling number of research confirm the possibility of using magnetic nanoparticles as highly effective and biocompatible drug carriers, ensuring the achievement of a sufficiently high intracellular concentration of drug and thus, increasing its antineoplastic activity. The results obtained so far indicate the possibility of the employment of natural AMPs and their synthetic analogs from ceragenins group in an effective eradication of cancer cells. Nevertheless, further studies aiming to elucidate the safety of proposed nanosystems and focused on the employment of ceragenin-based nanosystems in diagnostic MRI imaging and as hyperthermia inducers are needed and justified.


2022 ◽  
pp. 132345
Author(s):  
Mohammed Hawash ◽  
Deniz Cansen Kahraman ◽  
Abdurrahman Olgac ◽  
Sezen Guntekin Ergun ◽  
Ernest Hamel ◽  
...  

2021 ◽  
Vol 91 (11) ◽  
pp. 2280-2285
Author(s):  
Madhuri Pandiri ◽  
Satheesh Kumar Nukala ◽  
Gouthami Dasari ◽  
Vinitha Badithapuram ◽  
Srinivas Bandari

MedChemComm ◽  
2017 ◽  
Vol 8 (7) ◽  
pp. 1414-1420 ◽  
Author(s):  
Marcella Bassetto ◽  
Salvatore Ferla ◽  
Gilda Giancotti ◽  
Fabrizio Pertusati ◽  
Andrew D. Westwell ◽  
...  

A novel antiproliferative molecular scaffold was designed by rational modification of known antiandrogens, achieving a significant improvement in anti-cancer activity.


2020 ◽  
Vol 13 (1) ◽  
pp. 8 ◽  
Author(s):  
Eavan C. McLoughlin ◽  
Niamh M. O’Boyle

It is over 50 years since the discovery of microtubules, and they have become one of the most important drug targets for anti-cancer therapies. Microtubules are predominantly composed of the protein tubulin, which contains a number of different binding sites for small-molecule drugs. There is continued interest in drug development for compounds targeting the colchicine-binding site of tubulin, termed colchicine-binding site inhibitors (CBSIs). This review highlights CBSIs discovered through diverse sources: from natural compounds, rational design, serendipitously and via high-throughput screening. We provide an update on CBSIs reported in the past three years and discuss the clinical status of CBSIs. It is likely that efforts will continue to develop CBSIs for a diverse set of cancers, and this review provides a timely update on recent developments.


2019 ◽  
Vol 87 (4) ◽  
pp. 25 ◽  
Author(s):  
Stovbun ◽  
Ermakov ◽  
Bukhvostov ◽  
Vedenkin ◽  
Kuznetsov

Thio- and cyano- modified single-stranded poly(dNTP) sequences of different molecular sizes (20–200 n) and the same lengths routine poly(dNTP) and poly(NTP) species were tested for their impact on catalytic activities of β-like DNA polymerases from chromatin of HL-60, WERI-1A and Y-79 cells as well as for the affinity patterns in DNApolβ-poly(dNTP)/(NTP) pairs, respectively. An essential link between the lengths of ultrashort (50–100 n) single-stranded poly(dNTP) sequences of different structures and their inhibitory effects towards the cancer-specific DNA polymerases β was found. A possible significance of this phenomenon for both DNA repair suppression in tumors and a consequent anti-cancer activity of the DNA repair related short poly(dNTP) fragments is under discussion.


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