Theoretical insight of reactive oxygen species scavenging mechanism in lignin waste depolymerization products.

Apart from natural products and synthesis, phenolic compounds can be produced from the depolymerization of lignin, a major waste in biofuel and paper production. This process yields a plethora of aryl propanoid phenolic derivatives with broad biological activities, especially antioxidant properties. Due to its versatility, our study focuses on investigating the antioxidant mechanisms of several phenolic compounds obtained from renewable and abundant resources, namely, syringol (Hs), 4-allylsyringol (HAs), 4-propenylsyringol (HPns), and 4-propylsyringol (HPs). Employing the density functional theory (DFT) approach in conjunction with the QM-ORSA protocol, we aim to explore the reactivity of these compounds in neutralizing hydroperoxyl radicals in physiological and non-polar media. Kinetic and thermodynamic parameter calculations on the antioxidant activity of these compounds were also included in this study. Additionally, our research utilizes the activation strain model (ASM) for the first time to explain the reactivity of the HT and RAF mechanisms in the peroxyl radical scavenging process. It is predicted that HPs has the best rate constant in both media (1.13 × 108 M-1 s-1 and 1.75 × 108 M-1 s-1, respectively). Through ASM analysis, it is observed that the increase in the interaction energy due to the formation of intermolecular hydrogen bonds during the reaction is an important feature for accelerating the hydrogen transfer process. Furthermore, by examining the physicochemical and toxicity parameters, only Hs is not suitable for further investigation as a therapeutic agent because of potential toxicity and mutagenicity. However, overall, all compounds are considered potent HOO˙ scavengers in lipid-rich environments compared to previously studied antioxidants.

Bioactivity of dihydropyrimidinone derivatives as inhibitors of cyclooxygenase-2 (COX-2): an in silico approach.

Cyclooxygenase-2 (COX-2) is an enzyme involved in inflammation. The overexpression of COX-2 causes chronic inflammation, which can be prevented by COX-2 inhibitors. Generally, COX-2 inhibitors possess a carboxyl group and an aromatic ring in their molecular structure. These moieties are involved in the interaction with the active site of COX-2, thus playing a pivotal role in the inhibitory activity. Regarding the requisite molecular structure of COX-2 inhibitors, derivatives of dihydropyrimidinone (DHPM) are ideal candidates to be explored as COX-2 inhibitors, due to the ease of synthesis and their versatility to be transformed chemically. In this study, we prepared a novel small library consisting of 288 designed DHPM derivatives by varying the constituent components. The selection criteria of potential candidates for the COX-2 inhibitor of the data bank involve in silico studies via molecular docking investigations, prediction of ADMET and druglikeness, as well as molecular dynamics (MD) simulations. Molecular docking served as the initial step of selection, based on the comparison of grid score, docking pose, and interactions with those of lumiracoxib (LUR) as the original ligand of COX-2. The next criteria of selection were scores obtained from the ADMET and druglikeness by comparing the designed candidates with COX-2 inhibitors that were already marketed. Compound RDUE2 and SDT29 were the most potential candidates, which were further analyzed using the MD simulation. The results of the MD simulation indicated that RDUE2 and SDT29 interacted stably with amino acid residues on the active site of COX-2. The estimation of binding free energy indicated that SDT29 exhibited an inhibitory activity comparable to that of LUR, whereas RDUE2 showed a lower inhibitory activity than that of SDT29 and LUR.

Elucidation of reactive oxygen species scavenging pathways of norbergenin utilizing DFT approaches.

Bergenin is a polyphenolic compound that contains isocoumarin skeletal derived from C-glycosylated 4-O-methylgallic acid. The biological activities of this compound and its derivatives are quite diverse. Recent studies reveal neuroprotective effects in vitro and in vivo in Alzheimer's. Norbergenin is a demethylated form of bergenin, known for better antioxidant capacity and associated with neuroprotective properties through oxidative stress inhibition. This study focused on investigating the scavenging mechanism of norbergenin with the •OH, •OOH, and O 2 ∙ - as a radical model under physiological and lipid environments. The thermodynamic and kinetic parameters of the hydrogen transfer (HT), single electron transfer (SET), sequential proton lost-electron transfer (SPLET) and radical adduct formation (RAF) mechanisms were determined theoretically by the density functional theory (DFT) at M06-2X/6-311 + + G(d,p) level of theory. Based on the computational results, this compound has proved as an excellent •OOH and •OH scavenger under physiological conditions better than Trolox and vitamin C, whereas its radical demonstrated as an efficient O 2 ∙ - scavenger.

Clove Flower Extract (Syzygium aromaticum) Has Anticancer Potential Effect Analyzed by Molecular Docking and Brine Shrimp Lethality Test (BSLT).

Various anticancer medications have been discovered due to advances in the health care industry, but they have undesirable side effects. On the other hand, anticancer drugs derived from natural sources have low side effects, making them excellent for cancer therapy. This study aims to evaluate the effect of clove flower extract (Syzygium aromaticum) as a potential anticancer agent by determining grid-score values using molecular docking and LC50 values using the brine shrimp lethality test (BSLT) technique. As animal models, three hundred larvae of Artemia salina leach were divided into six groups. Each group has ten larvae that have undergone five replications. The clove flower extract concentration in the treatment media was 50 ppm (T1), 250 ppm (T2), 500 ppm (T3), 750 ppm (T4), 1000 ppm (T5), and 0 ppm (seawater) as the control. The probit analysis of Artemia Salina leach mortality percentage data. The results indicated that the clove flower extract (Syzygium aromaticum) is harmful to larvae with LC50 values of 227,1 g/ml or in the equation y = 2,8636 x - 1,7466 with an R2 value of 0.9062. According to molecular docking, eugenol acetate (grid-score -42.120834) has a close relationship with the cognate enzyme nitric oxide synthase (3E7G) based on its proximity to the grid score value (grid-score -61.271812). Therefore, clove flower extract has the potential to act as an anticancer medication. Based on the grid-score proximity, eugenol acetate is close to the homologous enzyme nitric oxide synthase (3E7G). Inhibition of nitric oxide synthase also shows a reduction in cancer cell proliferation.