Synthesis and biological evaluation of 2-alkoxycarbonylallyl esters as potential anticancer agents

Ronayne, Conor T.; Solano, Lucas N.; Nelson, Grady L.; Lueth, Erica A.; Hubbard, Skyler L.; Schumacher, Tanner J.; Gardner, Zachary; Jonnalagadda, Sravan K.; Gurrapu, Shirisha; Holy, Jon; Mereddy, Venkatram R.

doi:10.1016/j.bmcl.2017.01.037

Cited by 12 publications

(11 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhibition of MCT1 by MD1 is believed to block tumor growth through disruption of lactate transport and impairment of glycolysis while enhancing the oxidative phosphorylation metabolism (8,41). As a result, the observed 2P-FLIM of cellular NAD(P)H in 2D 4T1 culture is attributed to enhanced free NAD(P)H populations.…”

Section: Discussionmentioning

confidence: 99%

“…The novel cyano-4-hydroxycinnamic acid-based compound MD1 that inhibits MCT1 and MCT4 (8) and a triphenylphosphonium bromide derivative (TPPBr) that targets mitochondria (41,42) were used to examine the metabolic response of 4T1 in 2D and 3D cultures. The chemical structures of MD1 and TPPBr are shown in Figure 2.…”

Section: Novel Inhibitors Of Mctsmentioning

confidence: 99%

“…These compounds, currently being studied for their suitability as anticancer agents, include a cyano-4-hydroxycinnamic acid-based monocarboxylate transporter (MCT) inhibitor called MD1 (41), and an alkoxycarbonylallyl-based alkylator modified with a triphenylphosphonium group to target mitochondria and disrupt OXPHOS (42), called TPPBr. Toward this purpose, we report here the impact of a three-dimensional (3D) collagenous ECM on the metabolic responses of metastatic breast cancer cells to two novel inhibitors of MCTs and OXPHOS.…”

mentioning

confidence: 99%

“…Toward this purpose, we report here the impact of a three-dimensional (3D) collagenous ECM on the metabolic responses of metastatic breast cancer cells to two novel inhibitors of MCTs and OXPHOS. These compounds, currently being studied for their suitability as anticancer agents, include a cyano-4-hydroxycinnamic acid-based monocarboxylate transporter (MCT) inhibitor called MD1 (41), and an alkoxycarbonylallyl-based alkylator modified with a triphenylphosphonium group to target mitochondria and disrupt OXPHOS (42), called TPPBr.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Two‐photon fluorescence lifetime imaging of intrinsic NADH in three‐dimensional tumor models

et al. 2018

Self Cite

View full text Add to dashboard Cite

Most studies using intrinsic NAD(P)H as biomarkers for energy metabolism and mitochondrial anomalies have been conducted in routine two-dimensional (2D) cell culture formats. Cellular metabolism and cell behavior, however, can be significantly different in 2D cultures from that in vivo. As a result, there are emerging interests in integrating noninvasive, quantitative imaging techniques of NAD(P)H with in vivo-like threedimensional (3D) models. The overall features and metabolic responses of the murine breast cancer cells line 4T1 in 2D cultures were compared with those in 3D collagen matrix using integrated optical micro-spectroscopy. The metabolic responses to two novel compounds, MD1 and TPPBr, that target metabolism by disrupting monocarboxylate transporters or oxidative phosphorylation (OXPHOS), respectively, were investigated using two-photon fluorescence lifetime imaging microscopy (2P-FLIM) of intracellular NAD(P)H in 2D and 3D cultures. 4T1 cells exhibit distinct behaviors in a collagenous 3D matrix from those in 2D culture, forming anastomosing multicellular networks and spherical acini in 3D culture, as opposed to simple flattened epithelial plaques in 2D culture. The cellular NAD(P)H in 3D collagen matrix exhibits a longer fluorescence lifetime as compared with 2D culture, which is attributed to an enhanced population of enzyme-bound NAD(P)H in the 3D culture. TPPBr induces mitochondrial hyperpolarization in 2D culture of 4T1 cells along with an enhanced free NAD(P)H population, which suggest an interference with OXPHOS. In contrast, 2P-FLIM of cellular NAD(P)H revealed an enhanced autofluorescence lifetime in 3D 4T1 cultures after MD1 treatment as compared with MD1-treated 2D culture and the control 3D culture. Physical and chemical microenvironmental signaling are critical factors in understanding how therapeutic compounds target cancer cells by disrupting their metabolic pathways. Integrating 2P-FLIM of intrinsic NAD(P)H with refined 3D tumor-matrix in vitro models promises to advance our understanding of the roles of metabolism and metabolic plasticity in tumor growth and metastatic behavior. © 2018International Society for Advancement of Cytometry Key terms NAD(P)H; 4T1; 3D collagen matrix; MD1; TPPBr derivative; two-photon microscopy; FLIM CHANGES in cellular metabolism have long been recognized as a fundamental feature, and are now considered a hallmark, of cancer. A resurgent interest in this area has recently been driven in large measure by significant breakthroughs elucidating relevant mechanisms of cross-talk between not only tumor and stromal cells but also between distinct subpopulations of tumor cells themselves within heterogeneous tumors. In particular, advanced metabolic imaging methods promise to significantly enhance our understanding of how specific microenvironmental factors influence the regulation of cancer cell metabolism on a cell-by-cell basis. Overall, it is becoming clear that a better understanding of the metabolic features of cancer cells-and in particular those that may ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Novel Inhibitors Of Mctsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Two‐photon fluorescence lifetime imaging of intrinsic NADH in three‐dimensional tumor models

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…A standard sulforhodamine-B assay [ 30 , 31 ] was used to evaluate the cytotoxicity of the synthesized compounds on proliferating cancer cells. MCF-7 cells were cultured in 5% CO 2 atmosphere at 37°C in Iscove's Modified Dulbecco's medium containing 10% FBS and 1% antibiotic (penicillin-streptomycin).…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Evaluation of Baylis-Hillman Reaction Derived Imidazole and Triazole Cinnamates as Antifungal Agents

Nelson

Williams

Jonnalagadda

et al. 2018

International Journal of Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Allylic acetates derived from Baylis-Hillman reaction undergo efficient nucleophilic isomerization with imidazoles and triazoles to provide imidazolylmethyl and triazolylmethyl cinnamates stereoselectively. Antifungal evaluation of these derivatives against Cryptococcus neoformans exhibits good minimum inhibitory concentration values. These compounds exhibit low toxicity in proliferating MCF-7 breast cancer cell line. Structure activity relationship studies indicate that halogenated aromatic derivatives provide better antifungal activity.

show abstract

Synthesis and biological evaluation of novel 2-alkoxycarbonylallylester phosphonium derivatives as potential anticancer agents

Gardner

Schumacher

Ronayne

et al. 2021

Bioorganic & Medicinal Chemistry Letters

View full text Add to dashboard Cite

Synthesis and biological evaluation of 2-alkoxycarbonylallyl esters as potential anticancer agents

Cited by 12 publications

References 31 publications

Two‐photon fluorescence lifetime imaging of intrinsic NADH in three‐dimensional tumor models

Two‐photon fluorescence lifetime imaging of intrinsic NADH in three‐dimensional tumor models

Synthesis and Evaluation of Baylis-Hillman Reaction Derived Imidazole and Triazole Cinnamates as Antifungal Agents

Synthesis and biological evaluation of novel 2-alkoxycarbonylallylester phosphonium derivatives as potential anticancer agents

Contact Info

Product

Resources

About