Colchicine prodrugs and codrugs: Chemistry and bioactivities

Ghawanmeh, Abdullah A.; Chong, Kwok Feng; Sarkar, Shaheen M.; Bakar, Muntaz Abu; Othaman, Rizafizah; Khalid, Rozida Mohd.

doi:10.1016/j.ejmech.2017.12.029

Cited by 41 publications

(19 citation statements)

References 95 publications

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“…4D-H); however, we observed an increase in apical cell area () possibly due to an effect of colchicine on cell cycle progression and cell proliferation (Brues and Cohen, 1936; Ghawanmeh et al, 2018). In addition, colchicine did not affect cell shapes outside of the MHBC (…”

Section: Resultsmentioning

confidence: 66%

Basal epithelial tissue folding is mediated by differential regulation of microtubules

et al. 2018

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The folding of epithelial tissues is crucial for development of three-dimensional structure and function. Understanding this process can assist in determining the etiology of developmental disease and engineering of tissues for the future of regenerative medicine. Folding of epithelial tissues towards the apical surface has long been studied, but the molecular mechanisms that mediate epithelial folding towards the basal surface are just emerging. Here, we utilize zebrafish neuroepithelium to identify mechanisms that mediate basal tissue folding to form the highly conserved embryonic midbrain-hindbrain boundary. Live imaging revealed Wnt5b as a mediator of anisotropic epithelial cell shape, both apically and basally. In addition, we uncovered a Wnt5b-mediated mechanism for specific regulation of basal anisotropic cell shape that is microtubule dependent and likely to involve JNK signaling. We propose a model in which a single morphogen can differentially regulate apical versus basal cell shape during tissue morphogenesis.

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Section: Resultsmentioning

confidence: 66%

Basal epithelial tissue folding is mediated by differential regulation of microtubules

et al. 2018

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“…Nevertheless, semisynthetic derivatives that present lower toxicity have been developed and successfully applied on in vitro studies. Colchicinamide, deacetylcolchicine or valyl colchicine and other synthetic derivatives have been tested in different in vitro human cancer cell lines such as colorectal, chronic granulocytic leukemia, melanoma, central nervous system and breast cancers [36,[91][92][93]. It seems that deacetylcolchicine has been employed in clinical trials, due to its effectiveness against melanoma, Hodgkin's lymphoma, and chronic granulocytic leukemia [94], but, to our knowledge, no other clinical trials with colchicine derivatives have been reported.…”

Section: Colchicine Derivatesmentioning

confidence: 99%

Status and Challenges of Plant-Anticancer Compounds in Cancer Treatment

et al. 2021

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Nowadays, cancer is one of the deadliest diseases in the world, which has been estimated to cause 9.9 million deaths in 2020. Conventional treatments for cancer commonly involve mono-chemotherapy or a combination of radiotherapy and mono-chemotherapy. However, the negative side effects of these approaches have been extensively reported and have prompted the search of new therapeutic drugs. In this context, scientific community started to look for innovative sources of anticancer compounds in natural sources, including traditional plants. Currently, numerous studies have evaluated the anticancer properties of natural compounds derived from plants, both in vitro and in vivo. In pre-clinical stages, some promising compounds could be mentioned, such as the sulforaphane or different phenolic compounds. On the other hand, some phytochemicals obtained positive results in clinical stages and were further approved for cancer treatment, such as vinca alkaloids or the paclitaxel. Nevertheless, these compounds are not exempt of limitations, such as low solubility, restricted effect on their own, negative side-effects, etc. This review aims to compile the information about the current phytochemicals used for cancer treatment and also promising candidates, main action mechanisms and also reported limitations. In this sense, some strategies to face the limitations have been considered, such as nano-based formulations to improve solubility or chemical modification to reduce toxicity. In conclusion, although more research is still necessary to develop more efficient and safe phytochemical drugs, more of these compounds might be used in future cancer therapies.

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“…In order to obtain more effective microtubule inhibitors, we divided the molecule IC261 into Part A, Part B, and Part C ( Figure 4A) based on the interactions and the binding model between IC261 and tubulin. The methoxy group of 2,4,6-trimethoxyphenyl ring (Part A) has a similar structure to the 2,3,4-trimethoxyphenyl group of colchicine [25], which forms carbon hydrogen bond interactions with tubulin, suggesting that it is tolerable to adjust the position of the substituent of the methoxy group, but is not suitable for larger modifications. The C-C bond in the connection bridge (Part B) does not interact with any key amino acids, which shows the rationality of introducing amide, carbonyl, or other groups to explore the SAR and extend the chain appropriately.…”

Section: Insights Into Drug Design and Molecular Docking Studiesmentioning

confidence: 99%

A Rationale for Drug Design Provided by Co-Crystal Structure of IC261 in Complex with Tubulin

Xian

Wang

et al. 2021

Molecules

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Microtubules composed of α/β tubulin heterodimers are an essential part of the cytoskeleton of eukaryotic cells and are widely regarded as targets for cancer chemotherapy. IC261, which is discovered as an ATP-competitive inhibitor of serine/threonine-specific casein kinase 1 (CK1), has shown its inhibitory activity on microtubule polymerization in recent studies. However, the structural information of the interaction between tubulin and IC261 is still unclear. Here, we provided a high-resolution (2.85 Å) crystal structure of tubulin and IC261 complex, revealed the intermolecular interaction between tubulin and IC261, and analyzed the structure–activity relationship (SAR). Subsequently, the structure of tubulin-IC261 complex was compared with tubulin-colchicine complex to further elucidate the novelty of IC261. Furthermore, eight optimal candidate compounds of new IC261-based microtubule inhibitors were obtained through molecular docking studies. In conclusion, the co-crystal structure of tubulin-IC261 complex paves a way for the design and development of microtubule inhibitor drugs.

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Colchicine prodrugs and codrugs: Chemistry and bioactivities

Cited by 41 publications

References 95 publications

Basal epithelial tissue folding is mediated by differential regulation of microtubules

Basal epithelial tissue folding is mediated by differential regulation of microtubules

Status and Challenges of Plant-Anticancer Compounds in Cancer Treatment

A Rationale for Drug Design Provided by Co-Crystal Structure of IC261 in Complex with Tubulin

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