Potential Utilization of Phenolic Acid Compounds as Anti-Inflammatory Agents through TNF-α Convertase Inhibition Mechanisms: A Network Pharmacology, Docking, and Molecular Dynamics Approach.

Inflammation is a dysregulated immune response characterized by an excessive release of proinflammatory mediators, such as cytokines and prostanoids, leading to tissue damage and various pathological conditions. Natural compounds, notably phenolic acid phytocompounds from plants, have recently garnered substantial interest as potential therapeutic agents to bolster well-being and combat inflammation recently. Based on previous research, the precise molecular mechanism underlying the anti-inflammatory activity of phenolic acids remains elusive. Therefore, this study aimed to predict the molecular mechanisms underpinning the anti-inflammatory properties of selected phenolic acid phytocompounds through comprehensive network pharmacology, molecular docking, and dynamic simulations. Network pharmacology analysis successfully identified TNF-α convertase as a potential target for anti-inflammatory purposes. Among tested compounds, chlorogenic acid (-6.90 kcal/mol), rosmarinic acid (-6.82 kcal/mol), and ellagic acid (-5.46 kcal/mol) exhibited the strongest binding affinity toward TNF-α convertase. Furthermore, phenolic acid compounds demonstrated molecular binding poses similar to those of the native ligand, indicating their potential as inhibitors of TNF-α convertase. This study provides valuable insights into the molecular mechanisms that drive the anti-inflammatory effects of phenolic compounds, particularly through the suppression of TNF-α production via TNF-α convertase inhibition, thus reinforcing their anti-inflammatory attributes.

Synthesis, anti-angiogenic activity and prediction toxicity of (E)-3-(3-methoxyphenyl) propenoic acid.

Background: Anti-angiogenic medications, one of cancer chemo preventive mechanism were permitted for different cancers. Nevertheless, major primary and secondary resistance obstruct efficacy in several tumor types. Moreover, the improvement of safe and effective NSAIDs for angiogenesis inhibition is complicated, because of their serious toxicity. So, we require improving clinically appropriate strategies to boost efficacy of anti-angiogenic drugs with low risk of toxicity. Objectives: The present study aimed to synthesize the (E)-3- (3-methoxyphenyl)propenoic acid (3MPCA), to determine the anti-angiogenic activity and predict its toxicity. Methods: 3MPCA was obtained by Knoevenagel reaction using microwave irradiation at 400 Watt. The anti-angiogenesis experimental was performed using chorioallantois membrane of embryonated chicken eggs induced by b-FGF. The potency of 3MPCA was verified at dosage 30 and 60 ng and compared with celecoxib 60 ng. Toxicity prediction of 3MPCA was performed by ProTox II online program. Results: The results showed that 3MPCA was achieved in good yield (89%). Anti angogenic activity was showed by endothelial cells growth in neovascular capillaries of new blood vessel of chorioallantois membrane of embryonated chicken eggs. The endothelial cells growth decreased until 41.7-83%. The prediction LD50 was 1772mg/kg. Conclusion: (E)-3-(3-methoxyphenyl)propenoic acid can be obtained through Knovenagel reaction using microwave irradiation and it has potential as anti-angiogenesis inhibitor with low toxicity.

o-Hydroxycinnamic derivatives as prospective anti-platelet candidates: in silico pharmacokinetic screening and evaluation of their binding sites on COX-1 and P2Y12 receptors.

Background The high prevalence of thrombotic abnormalities has become a major concern in the health sector. This is triggered by uncontrolled platelet aggregation, which causes complications and death. The problem becomes more complicated because of the undesirable side effects of the drugs currently in use, some of which have reportedly become resistant. This study aims to evaluate the potency of o-hydroxycinnamic acid derivatives (OCA1a-22a) and their pharmacokinetic properties and toxicity for them to be developed as new antiplatelet candidates. Methods In silico analysis of pharmacokinetics was carried out using pKCSM. Molecular docking of the compounds OCA 1a-22a was performed using the Molegro Virtual Docker. In silico evaluation of the potency of biological activity was done by measuring the bonding energy of each tested compound to the target receptor i.e. COX-1 and P2Y12, as the Moldock score (MDS). Results pKCSM analyses showed that more than 90% of OCA 1a-22a are absorbed through the intestine and distributed in plasma. Most tested compounds are not hepatotoxic, and none is mutagenic. An evaluation of the COX-1 receptor showed that OCA 2a-22a have lower binding energy compared to aspirin, which is the COX-1 inhibitor used today. So, it can be predicted that OCA 2-22a have stronger activity. Interactions with P2Y12 show lower MDS than aspirin, but slightly higher than ibuprofen, which is the standard ligand. Conclusions ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile prediction shows that OCA 1a-22a have the potential to be developed as oral preparations. OCA 1a-22a have strong potential to interact with COX-1 and P2Y12 receptors, so they are prospective anti-platelet candidates.