Molecular docking and in silico evaluation of phytochemicals of bioactive methanolic extract of Ipomoea mauritiana Jacq. as anti-bacterial agents

Antibacterial treatment has grown difficult due to the increasing growth in bacterial infections, as well as their tolerance to most first-line antibiotics. This is a severe danger to the world’s human health in the 21st century, necessitating further research to identify drugs with improved antibacterial effects and broad-spectrum functions. This study aimed to discover anti-bacterial agents through the molecular docking and in silico approach. Most responsive thirty (32) compounds on UPLC-Q-TOF/MS analysis were selected from our previous report to get the hit compound(s) against inhibition of cell wall synthesis, inhibition of protein synthesis, interference with nucleic acid synthesis, inhibition of a metabolic pathway, inhibition of membrane function and inhibition of adenosine triphosphate (ATP) synthase. From the molecular docking results, we afforded six compounds for cell wall synthesis protein, four compounds for protein synthesis protein, five for nucleic acid synthesis protein, three for metabolic pathway protein, four for membrane function protein and three for ATP synthase protein which eventually undergoes the pharmacokinetic and drug-likeness properties to obtain lead compound(s). Finally, we discovered that compounds Turpinionosides B, Polydatin, Ledebouriellol, and Pterodontoside A have the strongest binding interactions with cell wall synthesis, inhibition of protein synthesis and inhibition of metabolic pathway synthesis, interference with nucleic acid synthesis and inhibition of ATP synthase, inhibition of membrane function proteins, respectively. These compounds have the potential to become an anti-bacterial therapeutic candidate due to their promising pharmacological properties

Pharmacophore-based molecular docking and in-silico study of novel usnic acid derivatives as avian influenza A (H7N9) inhibitor

The Avian Influenza virus is not only dangerous to birds, but it is also dangerous to people and other animals. It is a serious danger to poultry worldwide with the capacity to spread to other species, including people; consequently, more efficient medicines are required to treat this virus. This study examined the binding effectiveness of twentyone (21) Usnic acid derivatives out of 340 generated via pharmacophore filtering with AIV A (H7N9) utilising an in-silico technique. The docking simulation to AIV A obtained five compounds with a high affinity to the target protein. The ADMET and druggability prediction produced two lead molecules that were then submitted to Cytochrome (CYP) P450 enzyme screening to generate the best molecule, labelled as compound 5. According to the findings, compound 5 might be employed as a lead inhibitor in developing an anti-AIV medicatio

In silico evaluation of usnic acid derivatives to discover potential antibacterial drugs against DNA gyrase B and DNA topoisomerase IV

Due to the rising increase in infectious diseases brought on by bacteria and anti-bacterial drug resistance, antibacterial therapy has become difficult. The majority of first-line antibiotics are no longer effective against numerous germs, posing a new hazard to global human health in the 21st century. Through the drug-likeness screening, 184 usnic acid derivatives were selected from an in-house database of 340 usnic acid compounds. The pharmacokinetics (ADMET) prediction produced fifteen hit compounds, of which the lead molecule was subsequently obtained through a molecular docking investigation. The lead compounds, labelled compound-277 and compound-276, respectively, with the substantial binding affinity towards the enzymes were obtained through further docking simulation on the DNA gyrase and DNA topoisomerase proteins. Additionally, molecular dynamic (MD) simulation was performed for 300 ns on the lead compounds in order to confirm the stability of the docked complexes and the binding pose discovered during docking tests. Due to their intriguing pharmacological characteristics, these substances may be promising therapeutic candidate for anti-bacterial medication

Antidiabetic Effect of Actinodaphne angustifolia and Profiling of Bioactive Metabolites using UPLC-QToF/ESI-MS Method

Diabetes mellitus adalah gangguan kronik yang menyebabkan paras glukosa darah meningkat akibat kekurangan insulin, sama ada sepenuhnya atau sebahagian. Kami menyiasat sifat antidiabetik Actinodaphne angustifolia dalam model tikus dan mengenal pasti fitokimia bioaktif dengan menggunakan kaedah UPLC-QTOF/ ESI-MS. Struktur pankreas tikus, profil lipid dan glukosa darah dinilai selepas intervensi selama satu minggu. Analisis UPLC-QTOF/ESI-MS telah dijalankan untuk mengenal pasti flavonoid dan terpenoid dalam ekstrak daun. Ekstrak Actinodaphne angustifolia dengan ketara meningkatkan lipoprotein berketumpatan tinggi (HDL) (p<0.05) sambil mengurangkan jumlah kolesterol (TC), lipoprotein berketumpatan rendah (LDL) dan glukosa darah. Tambahan pula, struktur seni tisu pulau pankreas juga pulih dengan baik berbanding kumpulan kawalan. Sebanyak 45 flavonoid dan 109 sebatian terpenoid telah dikenal pasti menggunakan analisis berasaskan UPLC-QTOF/ESI-MS dan kajian tambahan perlu dijalankan untuk mengenal pasti agen antidiabetik yang berpotensi. Diabetes mellitus is a chronic disorder that causes elevated blood glucose levels due to a lack of insulin, either completely or partially. We investigated the antidiabetic property of Actinodaphne angustifolia in a rat model and identified the bioactive phytochemicals by using the UPLC-QTOF/ESI-MS method. The rats’ pancreatic structures, lipid profile and blood glucose were assessed after a one-week intervention. UPLC-QTOF/ESI-MS analysis was conducted to identify flavonoids and terpenoids in the leaf extract. Actinodaphne angustifolia extract markedly increased the high-density lipoprotein (HDL) (p<0.05) while reducing total cholesterol (TC), low-density lipoprotein (LDL) and blood glucose. Furthermore, the tissue architecture of pancreatic islets was also well recovered as compared to the control group. A total of 45 flavonoids and 109 terpenoid compounds were identified using UPLC-QTOF/ESI-MS-based analysis and additional studies should be undertaken to identify the potential antidiabetic agents

Identification of pyrazole derivatives of usnic acid as novel inhibitor of SARS-CoV-2 main protease through virtual screening approaches

The infection produced by the SARS-CoV-2 virus remains a significant health crisis worldwide. The lack of specific medications for COVID-19 necessitates a concerted effort to find the much-desired therapies for this condition. The main protease (Mpro) of SARS-CoV-2 is a promising target, vital for virus replication and transcription. In this study, fifty pyrazole derivatives were tested for their pharmacokinetics and drugability, resulting in eight hit compounds. Subsequent molecular docking simulations on SARS-CoV-2 main protease afforded two lead compounds with strong affinity at the active site. Additionally, the molecular dynamics (MD) simulations of lead compounds (17 and 39), along with binding free energy calculations, were accomplished to validate the stability of the docked complexes and the binding poses achieved in docking experiments. Based on these findings, compound 17 and 39, with their favorable projected pharmacokinetics and pharmacological characteristics, are the proposed potential antiviral candidates which require further investigation to be used as anti-SARS-CoV-2 medication

Pharmacophore-based virtual screening and in-silico study of natural products as potential DENV-2 RdRp inhibitors

Dengue fever is a significant public health concern throughout the world, causing an estimated 500,000 hospitalizations and 20,000 deaths each year, despite the lack of effective therapies. The DENV-2 RdRp has been identified as a potential target for the development of new and effective dengue therapies. This research’s primary objective was to discover an anti-DENV inhibitor using in silico ligand- and structure-based approaches. To begin, a ligand-based pharmacophore model was developed, and 130 distinct natural products (NPs) were screened. Docking of the pharmacophore-matched compounds were performed to the active site of DENV-2 RdRp protease . Eleven compounds were identified as potential DENV-2 RdRp inhibitors based on docking energy and binding interactions. ADMET and drug-likeness were done to predict their pharmacologic, pharmacokinetic, and drug-likeproperties . Compounds ranked highest in terms of pharmacokinetics and drug-like appearances were then subjected to additional toxicity testing to determine the leading compound. Additionally, MD simulation of the lead compound was performed to confirm the docked complex’s stability and the binding site determined by docking. As a result, the lead compound (compound-108) demonstrated an excellent match to the pharmacophore, a strong binding contact and affinity for the RdRp enzyme, favourable pharmacokinetics, and drug-like characteristics. In summary, the lead compound identified in this study could be a possible DENV-2 RdRp inhibitor that may be further studied on in vitro and in vivo models to develop as a drug candidate

Suppression of PGE2 production via disruption of MAPK phosphorylation by unsymmetrical dicarbonyl curcumin derivatives

Curcumin is an important molecule found in turmeric plants and has been reported to exhibit some profound anti-inflammatory activities by interacting with several important molecular targets found in the mitogen-activated protein kinase and NF-κβ pathways. As part of our continuing effort to search for new anti-inflammatory agents with better in vitro and in vivo efficacies, we have synthesized a series of new unsymmetrical dicarbonyl curcumin derivatives and tested their effects on prostaglandin E2 secretion level in interferon-γ/lipopolysaccharide-activated macrophage cells. Among those, five compounds exhibited remarkable suppression on prostaglandin E2 production with IC50 values ranging from 0.87 to 18.41 µM. The most potent compound 17f was found to down-regulate the expression of cyclooxygenase-2 mRNA suggesting that this series of compounds could possibly target the mitogen-activated protein kinase signal transduction pathway. Whilst the compound did not affect the expression of the conventional mitogen-activated protein kinases, the results suggest that it could disrupt the phosphorylation and activation of the proteins particularly the c-Jun N-terminal kinases. Finally, the binding interactions were examined using the molecular docking and dynamics simulation approaches