Optimizing the Distillation of Greek Oregano-Do Process Parameters Affect Bioactive Aroma Constituents and In Vitro Antioxidant Activity?

The aim of the present work was to optimize the conditions of the distillation process at a pilot scale to maximize the yield of specific bioactive compounds of the essential oil of oregano cultivated in Greece, and subsequently to study the in vitro antioxidant activity of these oils. Steam distillation was conducted at an industrial distillery and a Face-Centered Composite (FCC) experimental design was applied by utilizing three distillation factors: time, steam pressure and temperature. Essential oil composition was determined by static headspace gas chromatography-mass spectrometry (HS-GC/MS). To obtain a comprehensive profile of the essential oils, instrumental parameters were optimized, including sample preparation, incubation conditions, sampling process, injection parameters, column thermal gradient and MS conditions. With the applied GC-MS method, more than 20 volatile compounds were identified in the headspace of the oregano essential oils and their relative percentages were recorded. Carvacrol was the most prominent constituent under all distillation conditions applied. Data processing revealed time as the main factor which most affected the yield. The Desired Space (DSc) was determined by conducting a three-dimensional response surface analysis of the independent and dependent variables, choosing yields of thymol and carvacrol as optimization criteria. The in vitro antioxidant activity of the essential oils of all samples was measured in terms of the interaction with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) after 20 and 60 min. The most prominent essential oils at different distillation conditions were also tested as inhibitors of lipid peroxidation. Higher % values of carvacrol and thymol were correlated to higher antioxidant activity. Evaluating the impact of the distillation conditions on the in vitro results, it seems that lower pressure, less time and higher temperature are crucial for enhanced antioxidant activities.

Novel 3-aryl-5-substituted-coumarin analogues: Synthesis and bioactivity profile.

Eighteen 3-aryl-5-substituted-coumarins-six 5-acetyloxy-derivatives, six 5-hydroxy-derivatives, and six 5-geranyloxy-derivatives-were synthesized, structurally characterized and their antioxidant activity, lipoxygenase inhibitory ability, as well as their cytotoxic activity against human neuroblastoma SK-N-SH and HeLa adenocarcinoma cell lines were evaluated. The 5-acetyloxy-compounds 3a-3f were found to be the best cytotoxic agents among all the compounds studied. The bromo-substituted coumarins 3a and 3b were remarkably active against HeLa cell line showing IC50 1.8 and 6.1 µM, respectively. Coumarin 5e possessing a geranyloxy-chain on position 5 of the coumarin scaffold presented dual bioactivity, while 5-geranyloxy-coumarin 5f was the most competent soybean lipoxygenase inhibitor of this series (IC50 10 µM). As shown by in silico docking studies, the studied molecules present allosteric interactions with soybean lipoxygenases.

Curcumin in Health and Diseases: Alzheimer's Disease and Curcumin Analogues, Derivatives, and Hybrids.

Worldwide, Alzheimer's disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly preventing or treating AD. During the last decade, the scientific community has focused their research on the optimization of therapeutic properties and on the improvement of pharmacokinetic properties of curcumin. This review summarizes bibliographical data from 2009 to 2019 on curcumin analogues, derivatives, and hybrids, as well as their therapeutic, preventic, and diagnostic applications in AD. Recent advances in the field have revealed that the phenolic hydroxyl group could contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seem to contribute to the suppression of amyloid-ß peptide (Aß42) and to the suppression of amyloid precursor protein (APP) andhydrophobic interactions have also revealed a growing role. Furthermore, flexible moieties, at the linker, are crucial for the inhibition of Aß aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The promising role of curcumin-based compounds in diagnostic imaging is highlighted. The keto-enol tautomerism seems to be a novel modification for the design of amyloid-binding agents. Molecular docking results, (Q)SAR, as well as in vitro and in vivo tests highlight the structures and chemical moieties that are correlated with specific activity. As a result, the knowledge gained from the existing research should lead to the design and synthesis ofinnovative and multitargetedcurcumin analogues, derivatives, or curcumin hybrids, which would be very useful drug and tools in medicine for both diagnosis and treatment of AD.

Hybridization of Curcumin Analogues with Cinnamic Acid Derivatives as Multi-Target Agents Against Alzheimer's Disease Targets.

The synthesis of the new hybrids followed a hybridization with the aid of hydroxy-benzotriazole (HOBT) and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI.HCL) in dry DMF or thionyl chloride between curcumin analogues and cinnamic acid derivatives. IR, 1H-NMR, 13C-NMR, LC/MS ESI+, and elemental analysis were used for the confirmation of the structures of the novel hybrids. The lipophilicity values of compounds were calculated theoretically and experimentally via the reversed chromatography method as RM values. The novel derivatives were studied through in vitro experiments for their activity as antioxidant agents and as inhibitors of lipoxygenase, cyclooxygenase-2, and acetyl-cholinesterase. All the compounds showed satisfying anti-lipid peroxidation activity of linoleic acid induced by 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH). Hybrid 3e was the most significant pleiotropic derivative, followed by 3a. According to the predicted results, all hybrids could be easily transported, diffused, and absorbed through the blood-brain barrier (BBB). They presented good oral bioavailability and very high absorption with the exception of 3h. No inhibition for CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was noticed. According to the Ames test, all the hybrids induced mutagenicity with the exception of 3d. Efforts were conducted a) to correlate the in vitro results with the most important physicochemical properties of the structural components of the molecules and b) to clarify the correlation of actions among them to propose a possible mechanism of action. Docking studies were performed on soybean lipoxygenase (LOX) and showed hydrophobic interactions with amino acids. Docking studies on acetylcholinesterase (AChE) exhibited: (a) hydrophobic interactions with TRP281, LEU282, TYR332, PHE333, and TYR336 and (b) π-stacking interactions with TYR336.

Curcumin analogues and derivatives with anti-proliferative and anti-inflammatory activity: Structural characteristics and molecular targets.

Introduction: Curcumin (Diferuloylmethane) is a natural phenolic compound, which belongs to the curcuminoid family, presenting pleiotropic activity and low bioavailability. A lot of recent research is focused on the design and synthesis of curcumin analogs as antiproliferative and anti-inflammatory agents improving the bioavailability and target selectivity. Their structural characteristics and functional groups seem to define the extent of the biological activity. Areas covered: Publications (2008-2018), describing curcumin analogs and curcumin derivatives are analyzed. Structural characteristics, functional groups, modelling studies, structure activity relationships, biological evaluation in vitro/in vivo as antiproliferative and anti-inflammatory agents are included. Furthermore, a wide range of biological results derived from different targets are also summarized. Expert opinion: Several curcumin analogs and derivatives appear to have a high biological impact as well as promising antiproliferative and anti-inflammatory activities. Their clinical evaluation will be critical to assess therapeutic utility. Compounds for which the mechanism of action is well defined can serve as lead compounds for the design of new more potent molecules.