Heterocyclic Chalcone Analogues as Potential Anticancer Agents

Sharma, Vikas; Kumar, Vipin; Kumar, P. Sudheer

doi:10.2174/187152013804910424

Cited by 34 publications

(28 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In total, we synthesized and tested 23 CIT compounds that are structurally distinct from known chalcones with anticancer and anti-inflammatory activities. 5,[25][26][27][28] The discussions of structure-activity relationship (SAR) as well as the identifications of lead compounds, including CIT-026, will be reported separately.…”

Section: Cit-026 a Novel Cit Induces Cell Death In Cancer Cellsmentioning

confidence: 99%

Novel indolyl-chalcones target stathmin to induce cancer cell death

Węgiel

Jernigan

et al. 2016

Cell Cycle

View full text Add to dashboard Cite

Efficacy of current therapies for advanced and metastatic cancers remains a challenge in clinical practice. We investigated the anti-cancer potency of 3 novel indoly-chalcones (CITs). Our results indicated the lead molecule CIT-026 (Formula D C 20 H 16 FNO) induced cell death in prostate and lung cancer cell lines at sub-micromolar concentration. CITs (CIT-026, CIT-214, CIT-223) lead to microtubule destabilization, cell death and low cell proliferation, which in part was dependent on stathmin (STMN1) expression. Knockdown of STMN1 with siRNA against STMN1 in part restored viability of cancer cells in response to CITs. Further, CIT-026 and CIT-223 blocked cancer cell invasion through matrigel-coated chambers. Mechanistically, CITs inhibited phosphorylation of STMN1 leading to STMN1 accumulation and mitotic catastrophe. In summary, we have synthetized novel anti-cancer CIT molecules and defined their mechanism of action in vitro.

show abstract

Section: Cit-026 a Novel Cit Induces Cell Death In Cancer Cellsmentioning

confidence: 99%

Novel indolyl-chalcones target stathmin to induce cancer cell death

Węgiel

Jernigan

et al. 2016

Cell Cycle

View full text Add to dashboard Cite

show abstract

“…In particular incorporation of multiple electron releasing groups on ring-A with single or multiple electron releasing (or withdrawing) groups on ring-B [16], replacement of aryl rings with heteroaryl(s) [17], rigidification of keto vinyl arrangement to form chalconoids [18]. To the best of our knowledge most of the chalcones reported with anticancer action, both from the nature and synthesis typically contain more than one electron releasing group on ring-A [19][20][21][22][23][24], and even if monosubstitution is present it is either a simple -NH2, -OH, -OCH3 and -CH3 [25][26][27], but not a bulkier hydrophobic isobutyl functionality.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Characterization and Computational Evaluation of Novel Isobutychalcones as Cytotoxic Agents: Part-A

Shahanaaz³

2016

Preprint

View full text Add to dashboard Cite

A series of novel isobutylchalcones (A1-A20) were prepared, evaluated for their cytotoxic activity and characterized by FTIR, 1 H NMR, 13 C NMR, and elemental analysis data. The logic behind the design is to synthesize and compare chalcones containing electron releasing lipophilic isobutyl substituent on aromatic ring A and the B ring with aromatic ring containing a range of electron releasing and electron withdrawing groups as well as heteroaromatic rings for their cytotoxic activity. The compounds were tested against HT-29 (colon cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines using methotrexate (IC50 12 ± 1 (HT-29), 9 ±1 (MCF-7) 5 ± 1 (DU-145)) as reference standard. Compound A6 having 2,4-difluorphenyl moiety was most potent of the series against all the three cell lines and notably A6 was mainly effective against DU-145 cell lines with an IC50 value of 18 µg/mL. The critical structural features required for the activity against all the cell lines were identified through pharmacophore model using PHASE TM which has recognised a 5 point AHHRR model and is consistent with the cytotoxic activity of the tested compounds.

show abstract

“…indole, indolizine, oxazole, quinoline, isoquinoline etc for the treatment of the above mentioned ailments. [10][11][12] In the lights of these facts, Gundersen and coworkers 13 synthesized different indolizine derivatives for lipoxygenase inhibitory potential. Table 1 summarizes the 15-LOX inhibitory activity of indolizine derivatives.…”

Section: Introductionmentioning

confidence: 99%

Pharmacophore mapping studies on indolizine derivatives as 15-LOX inhibitors

Sharma¹,

Kumar²

2015

Bulletin of Faculty of Pharmacy, Cairo University

Self Cite

View full text Add to dashboard Cite

This investigation analyzes the common chemical features for 15-lipoxygenase (15-LOX) inhibitors to develop ligand-based pharmacophore models for lipoxygenase inhibitory activity. The present model is based on a dataset of 47 indolizine derivatives that exhibit inhibition against 15-LOX enzyme isolated from soybeans. Pharmacophore models were developed with pharmacophoric features namely: aromatic ring (R) and hydrogen bond acceptor (A). The pharmacophore hypothesis ARRR.5 with R 2 value 0.9451 yields a 3D-QSAR model which is statistically significant and the best pharmacophore hypothesis. External validation is performed to evaluate the robustness of the model and in this study; it was performed on a test set where correlation coefficient between experimental and predicted activity values was found to be 0.8508. The study suggested that pharmacophore modeling approach could be used as a tool for the development of lead structures.ª 2015 Production and hosting by Elsevier B.V. on behalf

show abstract

Heterocyclic Chalcone Analogues as Potential Anticancer Agents

Cited by 34 publications

References 0 publications

Novel indolyl-chalcones target stathmin to induce cancer cell death

Novel indolyl-chalcones target stathmin to induce cancer cell death

Design, Synthesis, Characterization and Computational Evaluation of Novel Isobutychalcones as Cytotoxic Agents: Part-A

Pharmacophore mapping studies on indolizine derivatives as 15-LOX inhibitors

Contact Info

Product

Resources

About