Anticancer activity of a novel small molecule tubulin inhibitor STK899704

Sakchaisri, Krisada; Kim, Sun Ok; Hwang, Joonsung; Soung, Nak-Kyun; Lee, Kyung Ho; Choi, Thomas Y.; Lee, Yong-Jun; Park, Chan Mi; Thimmegowda, N. R.; Lee, Phil Young; Shwetha, B.; Srinivasrao, Ganipisetti; Pham, Thi Thu Huong; Jang, Jae Hyuk; Yum, Hye Won; Surh, Young Joon; Lee, Kyung S.; Park, Hwangseo; Kim, Seung Jun; Kwon, Yong Tae; Ahn, Jong Seog; Kim, Bo Yeon

doi:10.1371/journal.pone.0173311

Cited by 34 publications

(33 citation statements)

References 46 publications

(54 reference statements)

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“…Further, if molecule binds, then there is a possibility of regulating the tubulin polymerization process. From docking calculation, it is shown that these molecules bind to tubulin dimer with 2 type of binding sides, (a) interface of dimer, which overlap the STK[41] and colchicine binding side and (b) α unit of tubulin which overlap the GTP binding side, whose major part is on the α unit of tubulin monomer (▶Fig. 4).…”

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Synthesis of Novel Diaziridinyl Quinone Isoxazole Hybrids and Evaluation of Their Anti-Cancer Activity as Potential Tubulin-Targeting Agents

et al. 2019

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Two series of diaziridinyl quinone isoxazole derivatives were prepared and evaluated for their cytotoxic activity against MCF7, HeLa, BT549, A549 and HEK293 cell lines and interaction with tubulin. Compounds (6a–m ) showed promising activity against all the 5 human cancer cell lines. Compounds 6a, 6e and 6 m were potent [IC50 ranging between 2.21 µg to 2.87 µg] on ER-positive MCF7 cell line similar to the commercially available drug molecule Doxorubicin. The results from docking models are in consistent with the experimental values which demonstrated the favourable binding modes of compounds 6a–m to the interface of α- and β-tubulin dimer.

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Synthesis of Novel Diaziridinyl Quinone Isoxazole Hybrids and Evaluation of Their Anti-Cancer Activity as Potential Tubulin-Targeting Agents

et al. 2019

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“…Microtubule-targeting agents such as the taxanes and the vinca alkaloids represent a successful class of anticancer drugs affect their dynamics by inhibiting cell proliferation. 29 Jacquemontia pentantha extract has antiproliferative effect on two tumor cell line namely (MCF-7 and HCT-116) is through affecting microtubulepolymer mass resulting in cell death. As cancer is a life-threating disease, phytol was found to exhibit a potent antitumor on MCF-7 breast cell line.…”

Section: Discussionmentioning

confidence: 99%

“…This was done according to, 12 as described by Mosmann T. 13 Following culturing for 10 days, the cells were seeded at concentration of 10×10 3 cells per well in case of MCF-7 and 20×103 cells/well in a fresh complete growth medium in case of HCT-116 cell lines, using 96-well 6,10,14,18,22-Tetracosahexaen-3-ol,2,6,10,15,19,23-hexamethyl (25,26,27,28,29,30)] respectively. Compound was confirmed by comparing its spectral data with squalene and its derivatives literature.…”

Section: Cell Viability Assaymentioning

confidence: 99%

“…1 HNMR [CDCl 3 : 600 MHz]: δ 5.10 [H:12, t, J = 3.5 Hz], 3.19 [H:3, dd, J = 5.0, 11.0 Hz], 1.01, 0.94, 0.93, 0.89, 0.72, 0.71 [CH 3(27,28,23,26,24,25), s], 0.85 [CH3: 29, d, J = 6.0 Hz], 0.74 [CH3: 30, d, J = 7.0 Hz]. , 42.1, 27.8, 26.5, 33.5, [C (11, 14, 15, 16, 17)] respectively, 59.2, 39.5, 39.5, 31.2, 41.5 [C (18, 19, 20, 21, 22)] respectively, 28.0, 15.6, 15.6, 16.9, 23.1 [C (23, 24, 25, 26, 27)] respectively, 28.7, 17.4, 21.3 [C(28,29,30)] respectively. The data for this compound was assigned by comparison with the corresponding in the published spectrum of α-Amyrin [21][22][23].…”

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Investigation of Secondary Metabolites and Cytotoxicity of Jacquemontia pentantha (Jacq.)

Eskander¹,

El-Khrisy²,

Grace³

et al. 2019

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Instrumentation NMR spectra were recorded on a Jeol Ex-600 MHz NMR spectrometer, using TMS as internal standard. UV spectrometer (Schimadzu UV-240) and mass spectra EI-MS (Varian MAT at 70ev) were used. Column chromatography (CC) was carried out on silica gel F254 (Merck) in glass blades. TLC was performed with silica gel 60 GF254 plates (Merck, Darmstadt, Germany), ABSTRACT Introduction: The aim of this study is to isolate and identify sterols and terpenes from the chloroform/methanol extract (3:1) of aerial parts of Jacquemontia pentantha (Jacq.) and evaluation of cytotoxic activity of crude extract and phytol for the first time from this plant. Methods: Different chromatographic techniques for the aerial parts of Jacquemontia pentantha extract were used resulting in isolation of eight compounds. Their structures were elucidated by spectroscopic methods including 1 HNMR, 13 CNMR, EI/MS spectrometry and by comparing their data with those reported in the literature. The cytotoxicity was evaluated using MTT assay. The mode of action of the extract was predicted by using Enzyme-linked Immunosorbent Assay Kit for Tubulin beta (TUBb). Results: Eight compounds for the first time from this plant were identified as Palmitic acid (1), Phytol (major) (2), Stigmast-4-en-3-one (3), mixture of α-amyrin (4) and β-amyrin (5), 1,6,10,14,18,2,6,10,15,19, (6) and mixture of α-amyrin acetate (7) and β-amyrin acetate (8). The extract showed potent cytotoxic activity on MCF-7 breast carcinoma cell line as well as HCT-116 colon carcinoma cell line at different concentrations (100-6.25 ug/ml) with IC 50 (21.8 ± 0.9) and (40.9 ± 1.3) respectively. Phytol showed potent cytotoxic activity on MCF-7 cell line at different concentrations (100-12.5 ug/ml) with IC 50 (60 ± 2.4), while it had no cytotoxic effect on HCT-116 cell line. The extract showed significant TUBb polymerization inhibition activity. Conclusion: The extract of aerial parts of Jacquemontia pentantha (Jacq.) and also phytol compound has cytotoxic activity due to the presence of phytochemicals such as sterols and terpenes. Eskander, et al.: Investigation of Secondary Metabolites and Cytotoxicity of Jacquemontia pentantha (Jacq.) GRAPHICAL ABSTRACT SUMMARY ABOUT AUTHORSThe aim of this study is to isolate and identify sterols and terpenes from the chloroform/methanol extract (3:1) of aerial parts of Jacquemontia pentantha (Jacq.) and evaluation of cytotoxic activity of crude extract and phytol for the first time from this plant. Different chromatographic techniques were used resulting in isolation of eight compounds for the first time from this plant, were identified as: Palmitic acid, Phytol (major), Stigmast-4-en-3-one, mixture of α-amyrin and β-amyrin, 1,6,10,14,18,2,6,10,15,19, and mixture of α-amyrin acetate and β-amyrin acetate .Their structures were elucidated by spectroscopic methods including 1 HNMR, 13 CNMR, EI/MS spectrometry and by comparing their data with those reported in the literature. Cytotoxicity was evaluated using MTT assay. Mode of action of extract was pr...

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“…In an effort to discover novel anticancer agents, we previously identified the small molecule STK899704 which has an acylhydrazone moiety known as a useful scaffold for drug development, especially for anticancer therapy due to its antimitotic activity . STK899704 inhibited microtubule polymerization leading to mitotic arrest and cell death.…”

Section: Introductionmentioning

confidence: 99%

A novel tubulin inhibitor STK899704 induces tumor regression in DMBA/TPA‐induced skin carcinogenesis model

Hwang

Soung

Han

et al. 2018

Experimental Dermatology

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Skin cancer is the most common type of cancer. The incidence rate of skin cancer has continuously increased over the past decades. In an effort to discover novel anticancer agents, we identified a novel tubulin inhibitor STK899704, which is structurally distinct from other microtubule-binding agents such as colchicine, vinca alkaloids and taxanes. STK899704 inhibited microtubule polymerization leading to mitotic arrest and suppressed the proliferation of various cancer cell lines as well as multidrug resistance cancer cell lines. In this study, our investigation is further extended into animal model to evaluate the effect of STK899704 on skin carcinogenesis in vivo. Surprisingly, almost 80% of the tumors treated with STK899704 were regressed with a one-fifth reduction in tumor volume. Furthermore, the efficacy of STK899704 was nearly 2 times higher than that of 5-fluorouracil, a widely used skin cancer therapeutic. Overall, our results suggest that STK899704 is a promising anticancer chemotherapeutic that may replace existing therapies, particularly for skin cancer.

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Anticancer activity of a novel small molecule tubulin inhibitor STK899704

Cited by 34 publications

References 46 publications

Synthesis of Novel Diaziridinyl Quinone Isoxazole Hybrids and Evaluation of Their Anti-Cancer Activity as Potential Tubulin-Targeting Agents

Synthesis of Novel Diaziridinyl Quinone Isoxazole Hybrids and Evaluation of Their Anti-Cancer Activity as Potential Tubulin-Targeting Agents

Investigation of Secondary Metabolites and Cytotoxicity of Jacquemontia pentantha (Jacq.)

A novel tubulin inhibitor STK899704 induces tumor regression in DMBA/TPA‐induced skin carcinogenesis model

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