Recent developments on (−)-colchicine derivatives: Synthesis and structure-activity relationship

Gloriosine, a colchicine-like natural product, is widely obtained from Gloriosa superba roots. Despite having remarkable anticancer potential, colchicine could not pave its way to the clinic, while gloriosine is yet to be investigated for its pharmacological effects. In the present work, 14 compounds, including gloriosine, were isolated from the G. superba roots and were characterized by NMR spectroscopy. Gloriosine ( 11 ) was evaluated for its antiproliferative activity against a panel of 15 human cancer cell lines of different tissues and normal breast cells. Gloroisine ( 11 ) displayed significant antiproliferative activity against various cancer cell lines selectively, with IC 50 values ranging from 32.61 to 100.28 nM. Further, gloriosine ( 11 ) was investigated for its apoptosis-inducing ability and found to form apoptotic bodies. It also inhibited A549 cell migration in the wound healing assay. Finally, molecular docking studies were performed to explore the possible binding modes of gloriosine with the colchicine-binding site of tubulin protein. Our findings suggested that gloriosine might be a potential lead for anticancer drug discovery.

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“… 7 Various semisynthetic modifications have been done to potentiate the anticancer activity of colchicine. 7 , 8 …”

Section: Introductionmentioning

confidence: 99%

Antiproliferative Potential of Gloriosine: A Lead for Anticancer Drug Development

et al. 2022

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“…When applying the Structure/Activity relationship (Ghawanmeh et al, 2020) to these molecules, we can assume that the three molecules have the same therapeutic effect (Thirumaran et al, 2019).…”

Section: Resultsmentioning

confidence: 99%

The Development of New Molecules Having Antiemetic Activity Using Molecular Modeling

Kanouni¹,

Benguerba²

2019

Current Research in Bioinformatics

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The solubility of a drug in water or in the blood represents the most desired parameter in medicine. Our aim is to obtain molecules with properties more effective than those of metoclopramide. In this work, two molecules with high solubility are constructed. Metoclopramide (a benzamide derivative) is a dopamine receptor antagonist used as an antiemetic drug. Its solubility in water is 200 mg/L at 25°C. In this work, we will develop two other molecules that have the same therapeutic activity of metoclopramide with a higher solubility in water, therefore in the blood, without affecting the other properties. The two molecules developed by molecular modeling with a chemical modification of the OH group of metoclopramide have a high solubility: approximately 3 times and 8 times that of metoclopramide. For the other physicochemical properties, there is a great similarity between the molecules. Thus, the two proposed molecules will have antiemetic activity, the second molecule will be more favorable because of its higher solubility and the number of HBA and HBD.

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“…Different functional groups, such as amides and thioamides, have been introduced in colchicine. An A-ring derivative, 4-halo-(-)-colchicine shows strong activity against human cancer cells, including lung adenocarcinoma A549, colon adenocarcinoma HT29, and HCT116, with the high selectivity and the low toxicity 205 .…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor pharmacology of natural products targeting mitosis

et al. 2022

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Cancer has been an insurmountable problem in the history of medical science. The uncontrollable proliferation of cancer cells is one of cancer’s main characteristics, which is closely associated with abnormal mitosis. Targeting mitosis is an effective method for cancer treatment. This review summarizes several natural products with anti-tumor effects related to mitosis, focusing on targeting microtubulin, inducing DNA damage, and modulating mitosis-associated kinases. Furthermore, the main disadvantages of several typical compounds, including drug resistance, toxicity to non-tumor tissues, and poor aqueous solubility and pharmacokinetic properties, are also discussed, together with strategies to address them. Improved understanding of cancer cell mitosis and natural products may pave the way to drug development for the treatment of cancer.

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Recent developments on (−)-colchicine derivatives: Synthesis and structure-activity relationship

Cited by 29 publications

References 49 publications

Antiproliferative Potential of Gloriosine: A Lead for Anticancer Drug Development

Antiproliferative Potential of Gloriosine: A Lead for Anticancer Drug Development

The Development of New Molecules Having Antiemetic Activity Using Molecular Modeling

Anti-tumor pharmacology of natural products targeting mitosis

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