Synthesis, biological evaluation and molecular docking studies of new amides of 4-bromothiocolchicine as anticancer agents

Klejborowska, Greta; Urbaniak, Alicja; Preto, Jordane; Maj, Ewa; Moshari, Mahshad; Wietrzyk, Joanna; Tuszyński, Jack A.; Chambers, Timothy C.; Huczyński, Adam

doi:10.1016/j.bmc.2019.115144

Cited by 8 publications

(13 citation statements)

References 59 publications

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“…The complete list of chosen natural compounds with their physiological charge was reported in the Supporting Information (Table S1). Then, ligand topologies were obtained with Antechamber [86,87] using the General Amber Force Field (GAFF) [86] and AM1-BCC charge method [88], as applied in previous studies [48,[89][90][91][92].…”

Section: Molecular Docking Protocolmentioning

confidence: 99%

The Impact of Natural Compounds on S-Shaped Aβ42 Fibril: From Molecular Docking to Biophysical Characterization

Muscat

Pallante

Stojceski

et al. 2020

IJMS

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The pursuit for effective strategies inhibiting the amyloidogenic process in neurodegenerative disorders, such as Alzheimer’s disease (AD), remains one of the main unsolved issues, and only a few drugs have demonstrated to delay the degeneration of the cognitive system. Moreover, most therapies induce severe side effects and are not effective at all stages of the illness. The need to find novel and reliable drugs appears therefore of primary importance. In this context, natural compounds have shown interesting beneficial effects on the onset and progression of neurodegenerative diseases, exhibiting a great inhibitory activity on the formation of amyloid aggregates and proving to be effective in many preclinical and clinical studies. However, their inhibitory mechanism is still unclear. In this work, ensemble docking and molecular dynamics simulations on S-shaped Aβ42 fibrils have been carried out to evaluate the influence of several natural compounds on amyloid conformational behaviour. A deep understanding of the interaction mechanisms between natural compounds and Aβ aggregates may play a key role to pave the way for design, discovery and optimization strategies toward an efficient destabilization of toxic amyloid assemblies.

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Section: Molecular Docking Protocolmentioning

confidence: 99%

The Impact of Natural Compounds on S-Shaped Aβ42 Fibril: From Molecular Docking to Biophysical Characterization

Muscat

Pallante

Stojceski

et al. 2020

IJMS

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“…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

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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.

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“…Several series of novel colchicine derivatives (Majcher et al, 2018a,b;Klejborowska et al, 2019) were considered in this work. All 55 compounds have shown in vitro anti-proliferative effects on normal and cancer cells.…”

Section: Atomic Models Of Investigated Compoundsmentioning

confidence: 99%

“…All 55 compounds have shown in vitro anti-proliferative effects on normal and cancer cells. In particular, they were tested on human lung adenocarcinoma, human breast adenocarcinoma, human colon adenocarcinoma cell lines and a doxorubicinresistant subline (Majcher et al, 2018a,b;Klejborowska et al, 2019).…”

Section: Atomic Models Of Investigated Compoundsmentioning

confidence: 99%

“…However, one of the main drawbacks of colchicine is its general toxicity (Wallace, 1974;Finkelstein et al, 2010). Several studies in the past have proposed less toxic colchicine derivatives as an alternative to colchicine (Lu et al, 2012;Wang et al, 2016;Johnson et al, 2017;Majcher et al, 2018a,b;Klejborowska et al, 2019). Moreover, these novel colchicine derivatives may be designed to show high specificity only for tubulin isotypes, which are over-expressed in cancer, in order to maximize their effect only on tumor cells and reduce side effects of the drug due to its toxicity on normal cells (Lu and Luduena, 1994;Luduena et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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In silico Investigations of the Mode of Action of Novel Colchicine Derivatives Targeting β-Tubulin Isotypes: A Search for a Selective and Specific β-III Tubulin Ligand

et al. 2020

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Synthesis, biological evaluation and molecular docking studies of new amides of 4-bromothiocolchicine as anticancer agents

Cited by 8 publications

References 59 publications

The Impact of Natural Compounds on S-Shaped Aβ42 Fibril: From Molecular Docking to Biophysical Characterization

The Impact of Natural Compounds on S-Shaped Aβ42 Fibril: From Molecular Docking to Biophysical Characterization

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

In silico Investigations of the Mode of Action of Novel Colchicine Derivatives Targeting β-Tubulin Isotypes: A Search for a Selective and Specific β-III Tubulin Ligand

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