Haloenol pyranones and morpholinones as antineoplastic agents of prostate cancer

Abstract

Haloenol pyran-2-ones and morpholin-2-ones were synthesized and evaluated as inhibitors of cell growth in two different prostate human cancer cell lines (PC-3 and LNCaP). Analogs derived from L- and D-phenylglycine were found to be the most effective antagonists of LNCaP and PC-3 cell growth. Additional studies reveal that the inhibitors induced G2/M arrest and the (S)-enantiomer of the phenylglycine-based derivatives was a more potent inhibitor of cytosolic iPLA2β.

Towards Lipidomics of Low-Abundant Species for Exploring Tumor Heterogeneity Guided by High-Resolution Mass Spectrometry Imaging

“…Most of these PLs belong to the phosphatidylcholine (PC) and phosphatidylethanolamine (PE) classes that are the most abundant PLs in mammalian cell membranes (40%–50% of total PLs for PC and 20%–50% for PE) [ 31 ]. The regulation of these PL species, notably in cellular membrane, has been associated with apoptosis [ 32 ], malignant transformation [ 33 ] and oxidative process [ 34 ]. In addition to the most abundant PC and PE detected, peaks with signal intensity barely detectable above the noise level are present and were considered for lipid mapping ( Tables 1 and 2 and examples in insets of Figures 2A and S1 ).…”

A Mild and Sustainable Procedure for the Functionalization of Morpholin-2-Ones by Oxidative Imidation Reactions

“…The morpholinones can be obtained from amino acid esters, for example, by reaction with an ethylene equivalent [38,39]. Morpholinones are very interesting compounds in their own right [40][41][42][43][44]. They are useful intermediates for the pharmaceutical industry, an example being the synthesis of Aprepitant (A, Figure 2), a drug utilized to prevent chemotherapy-induced nausea or vomiting [40].…”

Metal-Catalyzed Synthesis and Transformations of β-Haloenol Esters

“…In this context, while the utility of α-haloenol esters remains almost unexplored due to the lack of efficient and general synthetic methods [7][8][9][10], more accessible β-haloenol esters have gained significance in recent years as coupling partners in diverse chemical transformations. Several methodologies can be employed for the preparation β-haloenol esters, the most classical ones involving the acylation of haloenolate anions [11][12][13][14][15] or the haloacyloxylation of alkynes employing the elemental halogens [16][17][18][19][20], bis(pyridine)iodonium tetrafluoroborate (IPy 2 BF 4 ) [21][22][23][24][25], Haloenol lactones of type A and B (see Figure 2) are also a relevant class of compounds due to their biological activity as enzymes inhibitors [34][35][36][37][38], and also because they are a common structural motif in many natural products [39]. Access to these molecules is usually achieved by halolactonization of the corresponding alkynoic acid using I2, NBS, NIS or related halogenating agents, reactions that deliver the haloenol lactone products as the E isomers exclusively (Scheme 2) [34][35][36][37][38]40,41].…”

“…Mechanistic investigations indicated a bifunctional behavior of the organocatalysts, activating simultaneously the halogenating agent and the carboxylic acid unit. Haloenol lactones of type A and B (see Figure 2) are also a relevant class of compounds due to their biological activity as enzymes inhibitors [34][35][36][37][38], and also because they are a common structural motif in many natural products [39]. Access to these molecules is usually achieved by halolactonization of the corresponding alkynoic acid using I2, NBS, NIS or related halogenating agents, reactions that deliver the haloenol lactone products as the E isomers exclusively (Scheme 2) [34][35][36][37][38]40,41].…”

“…Haloenol lactones of type A and B (see Figure 2) are also a relevant class of compounds due to their biological activity as enzymes inhibitors [34][35][36][37][38], and also because they are a common structural motif in many natural products [39]. Access to these molecules is usually achieved by halolactonization of the corresponding alkynoic acid using I2, NBS, NIS or related halogenating agents, reactions that deliver the haloenol lactone products as the E isomers exclusively (Scheme 2) [34][35][36][37][38]40,41]. We would like also to highlight here that asymmetric versions of these halolactonization processes have been recently described employing cinchona alkaloid-based organocatalysts [42][43][44].…”