Potential anticancer role of colchicine-based derivatives

Kumar, Ashok; Sharma, Parduman R.; Mondhe, Dilip M.

doi:10.1097/cad.0000000000000464

Cited by 75 publications

(39 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fig 9 shows twelve natural products that were highly indexed as potential anticancer drug candidates by our ISE-based anticancer indexing model. Searching the scientific literature revealed that few of those molecules (Neoechinulin[ 38 ] , Colchicine[ 39 ], and Piperolactam[ 40 ]) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.…”

Section: Resultsmentioning

confidence: 99%

Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity

2017

View full text Add to dashboard Cite

Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

show abstract

Section: Resultsmentioning

confidence: 99%

Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity

2017

View full text Add to dashboard Cite

show abstract

“…In fact, cell cycle regulators have been strongly implicated in the progression of various tumors 26,27 , and disruption of cell cycle pathways including spindle assembly has been one of the main focus of current development of chemotherapy drugs [28][29][30] , for instance taxol and colchicine, which disrupts the microtubule polymerization dynamics, leading to inordinate spindle function and eventually cell death [31][32][33][34] .…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis Revealing Mitotic Spindle Assembly regulated NDC80 and MAD2L1 as Prognostic Biomarkers in Non-Small Cell Lung Cancer Development

Wei

Wang

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Lung cancer has been the leading cause of tumor related death, and 80%~85% of it is non-small cell lung cancer (NSCLC). Even with the rising molecular targeted therapies, for example EGFR, ROS1 and ALK, the treatment is still challenging. The study is to identify credible responsible genes during the development of NSCLC using bioinformatic analysis, developing new prognostic biomarkers and potential gene targets to the disease. Methods Firstly, three genes expression profiles GSE44077, GSE18842 and GSE33532 were picked from Gene Expression Omnibus (GEO) to analyze the genes with different expression level (GDEs) between NSCLC and normal lung samples, and the cellular location, molecular function and the biology pathways the GDEs enriched in were analyzed. Then, gene function modules of GDEs were explored based on the protein-protein interaction network (PPI), and the top module which contains most genes was identified, followed by containing genes annotation and survival analysis. Moreover, multivariate cox regression analysis was performed in addition to the Kaplan meier survival to narrow down the key genes scale. Further, the clinical pathological features of the picked key genes were explored using TCGA data. Results Three GEO profiles shared a total of 664 GDEs, including 232 up-regulated and 432 down-regulated genes. Based on the GDEs PPI network, the top function module containing a total of 69 genes was identified, and 31 of 69 genes were mitotic cell cycle regulation related. And survival analysis of the 31 genes revealed that 17/31 genes statistical significantly related to NSCLC overall survival, including 4 spindle assembly checkpoints, namely NDC80, BUB1B, MAD2L1 and AURKA. Further, multivariate cox regression analysis identified NDC80 and MAD2L1 as independent prognostic indicators in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively. Interestingly, pearson correlation analysis indicated strong connection between the four genes NDC80, BUB1B, MAD2L1 and AURKA, and their clinical pathological features were addressed. Conclusions Using bioinformatic analysis of GEO combined with TCGA data, we revealed two independent prognostic indicators in LUAD and LUSC respectively and analyzed their clinical features. However, more detailed experiments and clinical trials are needed to verify their drug targets role in clinical medical use.

show abstract

“…For this reason, new derivatives obtained through chemical modifications guided by structure-activity relations are intensively investigated. This research is aimed at reducing the colchicine toxicity and preserving the antimitotic and anticancer properties [12][13][14][15][16][17][18][19][20][21][22][23][24]. As it turns out, tubulin interacts with trimethoxyphenyl ring A and tropolone ring C, making the methoxy groups at C1, C2 and C10, as well as the C9-keto group, crucial for colchicine's antimitotic activity [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antiproliferative Screening Of Novel Analogs of Regioselectively Demethylated Colchicine and Thiocolchicine

et al. 2020

View full text Add to dashboard Cite

Colchicine, a pseudoalkaloid isolated from Colchicum autumnale, has been identified as a potent anticancer agent because of its strong antimitotic activity. It was shown that colchicine modifications by regioselective demethylation affected its biological properties. For demethylated colchicine analogs, 10-demethylcolchicine (colchiceine, 1) and 1-demethylthiocolchicine (3), a series of 12 colchicine derivatives including 5 novel esters (2b–c and 4b–d) and 4 carbonates (2e–f and 4e–f) were synthesized. The antiproliferative activity assay, together with in silico evaluation of physicochemical properties, confirmed attractive biological profiles for all obtained compounds. The substitutions of H-donor and H-acceptor sites at C1 in thiocolchicine position provide an efficient control of the hydration affinity and solubility, as demonstrated for anhydrate 3, hemihydrate 4e and monohydrate 4a.

show abstract

Potential anticancer role of colchicine-based derivatives

Cited by 75 publications

References 92 publications

Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity

Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity

Bioinformatic Analysis Revealing Mitotic Spindle Assembly regulated NDC80 and MAD2L1 as Prognostic Biomarkers in Non-Small Cell Lung Cancer Development

Synthesis and Antiproliferative Screening Of Novel Analogs of Regioselectively Demethylated Colchicine and Thiocolchicine

Contact Info

Product

Resources

About