5-Benzylidene-2,4-thiazolidenedione derivatives: Design, synthesis and evaluation as inhibitors of angiogenesis targeting VEGR-2

Bhanushali, Umesh; Rajendran, Saranya; Sarma, K V S S R S S; Kulkarni, Pushkar; Chatti, Kiranam; Chatterjee, Suvro; Ramaa, C. S.

doi:10.1016/j.bioorg.2016.06.006

Cited by 55 publications

(28 citation statements)

References 18 publications

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“…Activation of VEGFR2 results in the promotion of cell migration and vascular permeability. 33 In our study, gene expression of VEGFR2 was regulated by Stattic and Olanzapine in ECs. Furthermore, differences of gene expressions of MMP-2, MMP-9…”

Section: T a B L E 2 Fold Changes Of Gene Expressions Of Angiogenesismentioning

confidence: 50%

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The JAK/STAT3 signalling pathway regulated angiogenesis in an endothelial cell/adipose‐derived stromal cell co‐culture, 3D gel model

et al. 2016

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Section: T a B L E 2 Fold Changes Of Gene Expressions Of Angiogenesismentioning

confidence: 50%

“…VEGFR2 is a crucial VEGF‐kinase receptor which plays an important role in vascular development. Activation of VEGFR2 results in the promotion of cell migration and vascular permeability . In our study, gene expression of VEGFR2 was regulated by Stattic and Olanzapine in ECs.…”

Section: Discussionmentioning

confidence: 99%

The JAK/STAT3 signalling pathway regulated angiogenesis in an endothelial cell/adipose‐derived stromal cell co‐culture, 3D gel model

et al. 2016

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“…Synthesis of final compounds P1-P25 proceeded via four steps. The first step in the synthesis of variously substituted amides was as previously reported [23,[34][35][36][37]. Substituted amines 1a-1y were stirred overnight with chloroacetyl chloride in the presence of potassium carbonate (K 2 CO 3 ) and dichloromethane (DCM) as a solvent to produce 2a-2y.…”

Section: Chemistrymentioning

confidence: 99%

“…13 The 25 new derivatives of pyridyl containing N-substituted TZDs were synthesized as shown in Scheme 1. Variously substituted chloroacetylated amides (2a-2y) were prepared as previously reported [34][35][36][37]56,57]. All chloroacetylated amides were purified by recrystallization with suitable solvents and then used for the next reaction steps.…”

Section: Chemistrymentioning

confidence: 99%

Discovery of novel N-substituted thiazolidinediones (TZDs) as HDAC8 inhibitors: in-silico studies, synthesis, and biological evaluation

Upadhyay

Tilekar

Jänsch³

et al. 2020

Bioorganic Chemistry

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Epigenetics plays a fundamental role in cancer progression, and developing agents that regulate epigenetics is crucial for cancer management. Among Class I and Class II HDACs, HDAC8 is one of the essential epigenetic players in cancer progression. Therefore, we designed, synthesized, purified, and structurally characterized novel compounds containing N-substituted TZD (P1-P25). Cell viability assay of all compounds on leukemic cell lines (CEM, K-562, and KCL22) showed the cytotoxic potential of P8, P9, P10, P12, P19, and P25. In-vitro screening of different HDACs isoforms revealed that P19 was the most potent and selective inhibitor for HDAC8 (IC 50-9.3 μM). Thermal shift analysis (TSA) confirmed the binding of P19 to HDAC8. In-vitro screening of all compounds on the transport activity of GLUT1, GLUT4, and GLUT5 indicated that P19 inhibited GLUT1 (IC 50-28.2 μM). P10 and P19 induced apoptotic cell death in CEM cells (55.19% and 60.97% respectively) and P19 was less cytotoxic on normal WBCs (CC 50-104.2 μM) and human fibroblasts (HS27) (CC 50-105.0 μM). Thus, among this novel series of TZD *

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“…TZDs have exhibited antitumor activity in a wide variety of experimental cancer models by affecting cell cycle, induction of cell differentiation, and apoptosis, as well as by inhibiting tumor angiogenesis. [ 10,11 ] A study reported by Shah et al [ 12 ] showed that TZD derivative ciglitazone ( I ) (Figure 1) significantly decreased the VEGF production in human granulose cells in an in vitro model. Extensive studies were reported in the synthesis of several 5‐benzylidenethiazolidine‐2,4‐dione derivatives as potent anticancer agents [ 13–18 ] and potent vascular endothelial growth factor receptor‐2 (VEGFR‐2) inhibitors, for example, compound II .…”

Section: Introductionmentioning

confidence: 98%

5‐(4‐Methoxybenzylidene)thiazolidine‐2,4‐dione‐derived VEGFR‐2 inhibitors: Design, synthesis, molecular docking, and anticancer evaluations

El‐Adl

Sakr

Nasser

et al. 2020

Archiv der Pharmazie

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A novel series of 5‐(4‐methoxybenzylidene)thiazolidine‐2,4‐dione derivatives, 5a–g and 7a–f, was designed, synthesized, and evaluated for their anticancer activity against HepG2, HCT116, and MCF‐7 cells. HepG2 and HCT116 were the most sensitive cell lines to the influence of the new derivatives. In particular, compounds 7f, 7e, 7d, and 7c were found to be the most potent derivatives of all the tested compounds against the HepG2, HCT116, and MCF‐7 cancer cell lines. Compound 7f (IC50 = 6.19 ± 0.5, 5.47 ± 0.3, and 7.26 ± 0.3 µM, respectively) exhibited a higher activity than sorafenib (IC50 = 9.18 ± 0.6, 8.37 ± 0.7, and 5.10 ± 0.4 µM, respectively) against HepG2 and MCF‐7, cells but a lower activity against HCT116 cancer cells, respectively. Also, this compound displayed a higher activity than doxorubicin (IC50 = 7.94 ± 0.6, 8.07 ± 0.8, and 6.75 ± 0.4 µM, respectively) against HepG2 and MCF‐7 cells, but nearly the same activity against HCT116 cells, respectively. All derivatives, 5a–g and 7a–f, were evaluated for their inhibitory activities against vascular endothelial growth factor receptor‐2 (VEGFR‐2). Among them, compound 7f was found to be the most potent derivative that inhibited VEGFR‐2 at an IC50 value of 0.12 ± 0.02 µM, which is nearly the same as that of sorafenib (IC50 = 0.10 ± 0.02 µM). Compounds 7e, 7d, 7c, and 7b exhibited the highest activity, with IC50 values of 0.13 ± 0.02, 0.14 ± 0.02, 0.14 ± 0.02, and 0.18 ± 0.03 µM, respectively, which are more than the half of that of sorafenib. Furthermore, molecular docking was performed to investigate their binding mode and affinities toward the VEGFR‐2 receptor. The data obtained from the docking studies highly correlated with those obtained from the biological screening.

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5-Benzylidene-2,4-thiazolidenedione derivatives: Design, synthesis and evaluation as inhibitors of angiogenesis targeting VEGR-2

Cited by 55 publications

References 18 publications

The JAK/STAT3 signalling pathway regulated angiogenesis in an endothelial cell/adipose‐derived stromal cell co‐culture, 3D gel model

The JAK/STAT3 signalling pathway regulated angiogenesis in an endothelial cell/adipose‐derived stromal cell co‐culture, 3D gel model

Discovery of novel N-substituted thiazolidinediones (TZDs) as HDAC8 inhibitors: in-silico studies, synthesis, and biological evaluation

5‐(4‐Methoxybenzylidene)thiazolidine‐2,4‐dione‐derived VEGFR‐2 inhibitors: Design, synthesis, molecular docking, and anticancer evaluations

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