Design, synthesis, biological and in silico evaluation of coumarin-hydrazone derivatives as tubulin targeted antiproliferative agents

Govindaiah, Pilli; Dumala, Naresh; Mattan, Irshad; Grover, Paramjit; Prakash, M. Durga

doi:10.1016/j.bioorg.2019.103143

Cited by 38 publications

(27 citation statements)

References 32 publications

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“…Coumarin-3-formamido derivatives (2)(3)(4)(5)(6)(7)(8)(9)(10)(11) were synthesized by coumarin-3-ethyl formate (1) and benzylamine, benzylamine substituted with fluorine, benzylamine substituted with methoxy groups, 1-methyl-5-aminomethylimidazole, 2-thiophenemethylamine, and 2-furfurylamine by aminolysis of esters as reported. [31] The structures of the synthesized compounds were confirmed by infrared (IR; Figures S1-S11), nuclear magnetic resonance (NMR;…”

Section: Chemistrymentioning

confidence: 99%

“…On the basis of the IC 50 values (Table 1), a histogram ( Figure 3) was drawn to compare the antineoplastic activity and cytotoxicity of coumarin-3-ethyl formate (1), coumarin-3-formamide derivatives (2)(3)(4)(5)(6)(7)(8)(9)(10)(11), and DOX against axenic cancers cells more clearly.…”

Section: Antitumor Activitiesmentioning

confidence: 99%

“…[ 2,3 ] Chemotherapy is an effective method for treating cancer. [ 4–6 ] However, due to the resistance of tumor cells to multiple drugs, the effectiveness of drugs is greatly reduced, resulting in treatment failure. Therefore, overcoming the multidrug resistance of tumor cells [ 7–9 ] and searching for new antitumor drugs with high efficiency and low toxicity are important issues to be solved urgently.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, antiproliferative activities, and DNA binding of coumarin‐3‐formamido derivatives

Shi

Chen

et al. 2020

Archiv der Pharmazie

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Ten coumarin‐3‐formamido derivatives, N‐benzyl‐coumarin‐3‐carboxamide (2), N‐fluorobenzyl‐coumarin‐3‐carboxamide (3–5), N‐methoxybenzyl‐coumarin‐3‐carboxamide (6–8), N‐((1‐methyl‐1H‐imidazol‐5‐yl)methyl)‐coumarin‐3‐carboxamide (9), N‐(thiophen‐2‐ylmethyl)‐coumarin‐3‐carboxamide (10), and N‐(furan‐2‐ylmethyl)‐coumarin‐3‐carboxamide (11), were synthesized and characterized. Compound 5 crystallizes in a monoclinic system P21/c space group with four chemical formulas in a unit cell; molecules of compound 5 are self‐assembled into a two‐dimensional supramolecular structure by intermolecular hydrogen bonds and C⋯C π stacking. The potential anticancer effects of these compounds on HeLa (cervical carcinoma), MCF‐7 (breast), A549 (lung), HepG2 (liver), and human umbilical vein (HUVEC) cells were examined. Compared with compounds 1–8 and 10–11, compound 9 exhibits potent in vitro cytotoxicity against HeLa cells and lower cytotoxicity against normal cells. Therefore, further in‐depth investigations of compound 9 were performed. Absorption titration experiments and fluorescence spectroscopy studies suggested that compound 9 binds to DNA through the intercalation mode.

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Section: Chemistrymentioning

confidence: 99%

Section: Antitumor Activitiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis, antiproliferative activities, and DNA binding of coumarin‐3‐formamido derivatives

Shi

Chen

et al. 2020

Archiv der Pharmazie

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“…Coumarins are a wide family of secondary metabolites found in various species of plants but also fungi and microorganisms [3,4], which exhibit diverse pharmacological effects, especially anticancer activity [5][6][7]. Many coumarins and their derivatives have attracted considerable attention as cancer chemopreventive agents and also as cancer therapeutics [8][9][10][11][12][13][14]. Additionally, they have several attractive features, such as low molecular weight, simple structure, high bioavailability, high solubility in most of the organic solvents, and low toxicity, which ensure them a prominent role as lead compounds in drug research and development [15].…”

Section: Introductionmentioning

confidence: 99%

Coumarin Sulfonamides and Amides Derivatives: Design, Synthesis, and Antitumor Activity In Vitro

Zhang

Tan

et al. 2021

Molecules

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Coumarins possesses immeasurable antitumor potential with minimum side effects depending on the substitutions on the basic nucleus, which exhibits great prospects for antitumor drug development. In an attempt to develop novel antitumor candidates, a series of coumarin sulfonamides and amides derivatives were designed and synthetized. The majority of these derivatives showed good cytotoxic activity against MDA-MB-231 and KB cell lines, among which compound 9c was the most potent against MDA-MB-231 cells, with IC50 value of 9.33 μM, comparable to 5-fluorouracil. Further investigation revealed that compound 9c had versatile properties against tumors, including inhibition of cell migration and invasion as well as inducing apoptosis. Reactive oxygen species (ROS) assay and western blotting analysis suggested that compound 9c promoted cancer cell apoptosis by increasing ROS levels and upregulating the expression of caspase-3 in MDA-MB-231 cells. These results indicated that compound 9c could be promising lead compound for further antitumor drug research.

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“…The scaffold of coumarin had been widely used in drug design, especially in anticancer drugs [17][18][19] ( Figure 1). Actually, the targets of different anticancer coumarins vary much from each other, mainly involved carbonic anhydrase (isoforms IX and XII) [20][21][22][23] , STAT3 24 , tubulin 25 , topoisomerase II 26 , and BRD4 27 , etc. Dithiocarbamates (DTCs) is another important pharmacophore, which often be incorporated into the structure of antitumor agents, such as compound 1 28 (against MCF-7, MGC-823, SMMC-7721 and EC-9706 cell lines), compound 2 29 (against A549, MCF-7, Hela, HT-29 and HCT-116 cell lines), compound 3 30 (against A375, MGC-803, Hela, SMMC-7721, H1299 and HCT-116 cell lines), compound 4 31 (against A549 and HCT-116 cell lines), compound 5 32 (against leukaemia, non-small cell lung cancer, melanoma, etc.)…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents

Zhu

Ying

Zhou

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Colorectal cancer (CRC) is a common malignant tumour of human digestive tract. The high mortality rate of CRC is closely related to the limitations of existing treatments. Thus, there is an urgent need to search for new anti-CRC agents. In this work, twenty novel coumarin-dithiocarbamate derivatives (IDs) were designed, synthesized and evaluated in vitro. The results suggest that the most active compound ID-11 effectively inhibited the proliferation of CRC cell lines while shown little impact on normal colon epithelial cells. Mechanism studies revealed that ID-11 displayed bromodomain-containing protein 4 inhibitory activity, and induced G2/M phase arrest, apoptosis as well as decreased the expression levels of the key genes such as c-Myc and Bcl-2 in CRC cell lines. Moreover, the ADMET properties prediction results shown that ID-11 possess well metabolic characteristics without obvious toxicities. Our data demonstrated that compound ID-11 may be a promising anti-CRC agent and deserved for further development.

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Design, synthesis, biological and in silico evaluation of coumarin-hydrazone derivatives as tubulin targeted antiproliferative agents

Cited by 38 publications

References 32 publications

Synthesis, antiproliferative activities, and DNA binding of coumarin‐3‐formamido derivatives

Synthesis, antiproliferative activities, and DNA binding of coumarin‐3‐formamido derivatives

Coumarin Sulfonamides and Amides Derivatives: Design, Synthesis, and Antitumor Activity In Vitro

Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents

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