Design, Synthesis, and Characterization of Novel Series of Pharmacologically-important Sperm-shaped Amphiphilic Heterocyclic Compounds derived from Natural Palmitic Acid

Natural palmitic acid is a pivotal saturated fatty acid used in many biochemical processes occurring in humans and diverse living creatures, as it is the most common natural long-chain carboxylic acid whose unrivaled amphiphilic sperm-like skeleton with the inert single 15-C aliphatic chain (tail or carrier) and the very active one carboxyl group (head) represent a rich reactive entity and carrier for several organic/medicinal chemistry and pharmaceutics applications with respect to drug design and formulation. Derivatives of 1,3,4-oxadiazoles along with their 1,3,4-thiadiazoles and 1,2,4-triazoles analogs exhibit a broad spectrum of substantial pharmacological activities. Agreeing with the well-known hybridization principles and incorporation norms in hybrid chemistry, if a substituted nitrogenous heterocyclic aromatic nucleus of the three aforementioned kinds is straightway attached to the simple straight palmitic acid backbone at the position of the carboxyl group, the produced molecules are supposed to be very bioactive. This research work reports for the first once the efficient design/synthesis and characterization/elucidation of four one-tailed nitrogen-containing heterocyclic derivatives of palmitic acid constructure, which introduce a novel biologically-important pharmacophore having biocompatible amphiphilic sperm-shaped heteroaromatic structure.

C/EBPB-dependent adaptation to palmitic acid promotes tumor formation in hormone receptor negative breast cancer

Epidemiological studies have established a positive association between obesity and the incidence of postmenopausal breast cancer. Moreover, it is known that obesity promotes stem cell-like properties of breast cancer cells. However, the cancer cell-autonomous mechanisms underlying this correlation are not well defined. Here we demonstrate that obesity-associated tumor formation is driven by cellular adaptation rather than expansion of pre-existing clones within the cancer cell population. While there is no correlation with specific mutations, cellular adaptation to obesity is governed by palmitic acid (PA) and leads to enhanced tumor formation capacity of breast cancer cells. This process is governed epigenetically through increased chromatin occupancy of the transcription factor CCAAT/enhancer-binding protein beta (C/EBPB). Obesity-induced epigenetic activation of C/EBPB regulates cancer stem-like properties by modulating the expression of key downstream regulators including CLDN1 and LCN2. Collectively, our findings demonstrate that obesity drives cellular adaptation to PA drives tumor initiation in the obese setting through activation of a C/EBPB dependent transcriptional network.

Development of “NEC-SD-LAMP,” a New Non-Electrified Infectious Diseases Testing Method

Here, non-electric-control SalivaDirect loop-mediated isothermal amplification (NEC-SD-LAMP), which can detect infections by analyzing viral gene expression in saliva without electrical control systems, was developed. In this method, viral genes are purified from saliva using SalivaDirect, and gene expression is analyzed by loop-mediated isothermal amplification (LAMP) by adding water to the device, and the results can be visually confirmed. Melting palmitic acid maintains the optimal temperature for the LAMP reaction, as the temperature of palmitic acid is maintained at 62.9°C, its melting point. By taking advantage of the proximity of this melting point to the optimal temperature for LAMP, it is possible to perform LAMP without electricity. Using this method, adenovirus DNA was detected in saliva. Furthermore, the detection limit was 2 copies per µL, indicating that it is possible to detect viral infections in saliva even before the onset of SARS-CoV-2 infection.

Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites

Polyunsaturated fatty acids (PUFAs) inhibit pentameric ligand-gated ion channels (pLGICs) but the mechanism of inhibition is not well understood. The PUFA, docosahexaenoic acid (DHA), inhibits agonist responses of the pLGIC, ELIC, more effectively than palmitic acid, similar to the effects observed in the GABAA receptor and nicotinic acetylcholine receptor. Using photo-affinity labeling and coarse-grained molecular dynamics simulations, we identified two fatty acid binding sites in the outer transmembrane domain (TMD) of ELIC. Fatty acid binding to the photolabeled sites is selective for DHA over palmitic acid, and specific for an agonist-bound state. Hexadecyl-methanethiosulfonate modification of one of the two fatty acid binding sites in the outer TMD recapitulates the inhibitory effect of PUFAs in ELIC. The results demonstrate that DHA selectively binds to multiple sites in the outer TMD of ELIC, but that state-dependent binding to a single intrasubunit site mediates DHA inhibition of ELIC.

Biochemical parameters and antioxidant property of three Salvia L. taxa endemic in Turkey

The aim of the present study was to determine and compare the fatty acids, lipid soluble vitamins, sterols, phenolics, and antioxidant capacities of three endemic Salvia L. taxa (S. euphratica var. Montbret & Aucher ex Bentham leiocalycina (Rech. Fil.) Hedge, S. euphratica var. Montbret & Aucher ex Bentham euphratica (Rech. Fil.) Hedge and S. pseudoeuphratica Rech.Fil.) and to evaluate these results systematically. The fatty acid compositions were determined by using gas chromatography, while the lipid soluble vitamins, sterols, and phenolics were determined by using HPLC. Also, the antioxidant capacities of three Salvia taxa were measured in vitro. Palmitic acid was found as major saturated fatty acid while oleic acid, linoleic acid, α-linolenic acid, and erucic acid were found as major unsaturated fatty acids in the present study. It was found that S. euphratica var. euphratica had lower palmitic acid (8.94 ± 0.71%), total saturated fatty acid (19.16 ± 0.15%), and higher unsaturated fatty acid content (82.08 ± 0.52%) than other studied taxa. Furthermore, it was shown that S. euphratica var. euphratica had different 18.3/18:2 (0.36) unsaturated/saturated fatty acid (4.28) ratios. However, this study demonstrated that Salvia taxa had low lipid soluble vitamins, sterol contents. On the other hand, it was shown that Salvia taxa had similar catechin (509.2 ± 4.21 µg/g and 552.2 ± 9.21 µg/g) and vanillic acid amounts (351.2 ± 2.17 µg/g and 396.8 ± 4.1 µg/g) in this study. And also, it was found that Salvia taxa had high rosmarinic acid content while S. euphratica var. leiocalycina had the highest rosmarinic acid content (1480 ± 7.57 µg/g). On the other hand, it was shown that the two ferulic acid contents of S. euphratica varieties were higher (1175 ±/5.21 µgmg-1740.2 ± 4.82 µg/mg) than the ferulic acid content of S. pseudoeuphratica of which was the lowest (19.2 ± 0.97 µg/mg). The present results suggested that the biochemical results guided the morphological studies, and Salvia taxa have a potent antioxidant capacity.