Eco-friendly synthesis of new olanzapine derivatives and evaluation of their anticancer potential.

New derivatives of the known antipsychotic drug olanzapine have been obtained as potential compounds with anticancer activity in two metabolically different breast cancer cell lines: MCF-7 and triple negative MDA-MB-231. The compounds were obtained under phase transfer catalysis (PTC) in the presence of microwave irradiation (MW) or ultrasound (")))"), evaluating the effect of solvents such as dimethylformamide, water, or choline chloride/urea (natural deep eutectic solvent, NaDES). In the best option, the compounds were obtained within 2 minutes with a yield of 57-86% in MW. Two of the obtained compounds which have a naphthalimide moiety and a pentyl (7) or hexyl chain (8) show pronounced cytotoxicity. Interestingly, neither olanzapine nor desmethylolanzapine (DOLA), which was one of the substrates for the synthesis reaction, showed any significant activity in the study.

"Novel chitosan/alginate hydrogels as carriers of phenolic-enriched extracts from saffron floral by-products using natural deep eutectic solvents as green extraction media".

The current saffron production system is generating several hundreds of tons of tepal waste, because only stigmas are used for food. Consequently, the valorization of saffron floral by-products by developing stable functional ingredients could lead to the environmental impact minimization. Thus, the main aim of this study was to develop innovative green extraction processes from saffron floral by-products by using Natural Deep Eutectic Solvents (NaDES) and ultrasound-assisted extraction (UAE) as ecological extraction method. Response surface methodology was used to optimize process parameters. To improve the stability of the optimal extracts, they were incorporated into chitosan/alginate hydrogels, studying their water-uptake and water retention capacity and the total phenolic content (TPC) during the in vitro digestion. The results indicated that the optimal extraction, regarding total phenolic and flavonoid content, was achieved in 20 min, using 180 W ultrasound power and 90% of NaDES. The results of the DPPH assay revealed the potent antioxidant activity of saffron floral by-products. The chitosan/alginate hydrogels incorporating the as-obtained NaDES extracts showed favorable properties whereas the TPC remained stable under intestinal conditions. Therefore, NaDES combined with UAE was an efficient technique to isolate high added-value compounds from saffron flowers, succeeding also the valorization of discarded waste by using green and low-cost strategies. Furthermore, these novel hydrogels could be used as promising candidates for food or cosmetic applications.

Novel Multi-Target Agents Based on the Privileged Structure of 4-Hydroxy-2-quinolinone.

In this work, the privileged scaffold of 4-hydroxy-2quinolinone is investigated through the synthesis of carboxamides and hybrid derivatives, as well as through their bioactivity evaluation, focusing on the ability of the molecules to inhibit the soybean LOX, as an indication of their anti-inflammatory activity. Twenty-one quinolinone carboxamides, seven novel hybrid compounds consisting of the quinolinone moiety and selected cinnamic or benzoic acid derivatives, as well as three reverse amides are synthesized and classified as multi-target agents according to their LOX inhibitory and antioxidant activity. Among all the synthesized analogues, quinolinone-carboxamide compounds 3h and 3s, which are introduced for the first time in the literature, exhibited the best LOX inhibitory activity (IC50 = 10 µM). Furthermore, carboxamide 3g and quinolinone hybrid with acetylated ferulic acid 11e emerged as multi-target agents, revealing combined antioxidant and LOX inhibitory activity (3g: IC50 = 27.5 µM for LOX inhibition, 100% inhibition of lipid peroxidation, 67.7% ability to scavenge hydroxyl radicals and 72.4% in the ABTS radical cation decolorization assay; 11e: IC50 = 52 µM for LOX inhibition and 97% inhibition of lipid peroxidation). The in silico docking results revealed that the synthetic carboxamide analogues 3h and 3s and NDGA (the reference compound) bind at the same alternative binding site in a similar binding mode.

Synthesis, Conformational Analysis and ctDNA Binding Studies of Flavonoid Analogues Possessing the 3,5-di-tert-butyl-4-hydroxyphenyl Moiety.

Flavanones and their biochemical precursors, chalcones, are naturally occurring compounds and consist of privileged scaffolds used in drug discovery due to their wide range of biological activities. In this work, two novel flavanones (3 and 4), the arylidene flavanone 5, and the chalcone 6, displaying structural analogies with butylated hydroxytoluene (BHT), were synthesized via an aldol reaction. According to the antioxidant activity studies of the synthesized flavanones, the arylidene flavanone 5 was the most potent antioxidant (70.8% interaction with DPPH radical and 77.4% inhibition of lipid peroxidation). In addition, the ability of the synthesized compounds to bind with ctDNA was measured via UV-spectroscopy, revealing that chalcone 6 has the strongest interaction with DNA (Kb = 5.0 × 10-3 M-1), while molecular docking was exploited to simulate the compound-DNA complexes. In an effort to explore the conformational features of the novel synthetic flavanones (3 and 4), arylidene flavanone 5, and chalcone 6, theoretical calculations were applied and the calculation of their physicochemical properties was also performed.

Exploring the 2'-Hydroxy-Chalcone Framework for the Development of Dual Antioxidant and Soybean Lipoxygenase Inhibitory Agents.

2'-hydroxy-chalcones are naturally occurring compounds with a wide array of bioactivity. In an effort to delineate the structural features that favor antioxidant and lipoxygenase (LOX) inhibitory activity, the design, synthesis, and bioactivity profile of a series of 2'-hydroxy-chalcones bearing diverse substituents on rings A and B, are presented. Among all the synthesized derivatives, chalcone 4b, bearing two hydroxyl substituents on ring B, was found to possess the best combined activity (82.4% DPPH radical scavenging ability, 82.3% inhibition of lipid peroxidation, and satisfactory LOX inhibition value (IC50 = 70 µM). Chalcone 3c, possessing a methoxymethylene substituent on ring A, and three methoxy groups on ring B, exhibited the most promising LOX inhibitory activity (IC50 = 45 µM). A combination of in silico techniques were utilized in an effort to explore the crucial binding characteristics of the most active compound 3c and its analogue 3b, to LOX. A common H-bond interaction pattern, orienting the hydroxyl and carbonyl groups of the aromatic ring A towards Asp768 and Asn128, respectively, was observed. Regarding the analogue 3c, the bulky (-OMOM) group does not seem to participate in a direct binding, but it induces an orientation capable to form H-bonds between the methoxy groups of the aromatic ring B with Trp130 and Gly247.

Nanosystems for the Encapsulation of Natural Products: The Case of Chitosan Biopolymer as a Matrix.

Chitosan is a cationic natural polysaccharide, which has emerged as an increasingly interesting biomaterialover the past few years. It constitutes a novel perspective in drug delivery systems and nanocarriers' formulations due to its beneficial properties, including biocompatibility, biodegradability and low toxicity. The potentiality of chemical or enzymatic modifications of the biopolymer, as well as its complementary use with other polymers, further attract the scientific community, offering improved and combined properties in the final materials. As a result, chitosan has been extensively used as a matrix for the encapsulation of several valuable compounds. In this review article, the advantageous character of chitosan as a matrix for nanosystemsis presented, focusing on the encapsulation of natural products. A five-year literature review is attempted covering the use of chitosan and modified chitosan as matrices and coatings for the encapsulation of natural extracts, essential oils or pure naturally occurring bioactive compounds are discussed.

Green biotransformations catalysed by enzyme-inorganic hybrid nanoflowers in environmentally friendly ionic solvents.

Environmentally friendly ionic solvents such as (a) ionic liquids (ILs) formulated with hydroxyl ammonium cations and various carboxylic acid anions and (b) choline chloride or ethyl ammonium chloride-based deep eutectic solvents (DES) were tested as media for hydrolytic and synthetic reactions catalysed by lipase-inorganic hybrid nanoflowers. The nature of ionic solvents used has a significant effect on the hydrolytic and synthetic activity of the immobilized lipase, as well as on its stability and reusability. In choline chloride-based DES, the activity and especially the operational stability of the biocatalyst are significantly increased compared to those observed in buffer, indicating the potential application of these solvents as green media for various biocatalytic processes of industrial interest.