Comprehensive pharmacognostic evaluation, bioactive compound isolation, structural elucidation, and in silico analysis of Cissus quadrangularis L.

This research involves the development, synthesis, in-silico ADMET and molecular docking studies, and in-vitro anti-inflammatory analysis of chalcone-linked pyrazole amine compounds. This study focuses on the synthesis of pyrazole-fused chalcone amine derivatives via molecular hybridization. Two synthetic series were designed, each using different hydrazide and amine derivatives, resulting in a library of 100 compounds. In-silico ADMET analysis and molecular docking studies were conducted via different tools for all compounds, leading to the selection of six derivatives based on their scores. These selected compounds were synthesized and subsequently evaluated in-vitro for anti-inflammatory activity using the egg albumin protein denaturation method. The structural identification of the synthesized chalcone-linked pyrazole amine derivatives was confirmed through FT-IR, 1H NMR, 13C NMR, and MASS, with the observed peaks consistent with the expected products. These compounds were selected based on favorable ADMET and molecular docking scores obtained from in-silico analyses using various computational tools. In-vitro anti-inflammatory evaluation suggests that these derivatives hold significant potential as anti-inflammatory agents, likely due to the synergistic effects of the pyrazole-fused chalcone moiety. In conclusion, pyrazole-fused chalcone amine derivatives were successfully synthesized and validated, showing promising in-silico and in-vitro anti-inflammatory activity, making them potential candidates for further development as anti-inflammatory agents.

Nutritional, Anti-inflammatory, and in-silico inhibitory Studies of Trametes versicolor (L.) Lloyd and Flammulina velutipes (Curtis) on HER2 breast cancer protein.

Swertiamarin, a natural steroid, prevent bone erosion by modulating RANKL/RANK/OPG signaling

Abstract. Mohanty SK, Nayak Y, Sahoo L. 2024. Comprehensive phytochemical analysis of Momordica charantia ethanol extract: Insights from Gas Chromatography-Mass Spectroscopy and in-silico ADMET studies. Asian J Agric 8: 1-9. The Momordica charantia L. plant, also known as bitter gourd or bitter melon, is a crucial herbal remedy with a wide range of medicinal properties. It contains various essential phytocompounds, which contribute to its anti-inflammatory, antioxidant, and neuroprotective. The study investigates the phytochemical profile of M. charantia (bitter melon) ethanol extract using Gas Chromatography-Mass Spectrometry (GC-MS) analysis, coupled with an in-silico ADMET assessment of the identified compounds. GC-MS analysis revealed a diverse range of phytoconstituents, including bioactive compounds such as Vitamin E, gentisic acid, cucurbitacin B dihydro, and various fatty acid esters, known for their potential therapeutic benefits. These compounds were further analysed using in-silico ADMET tools to predict their pharmacokinetic & Physiochemistry profiles. The results indicated that the majority of the identified compounds possess favourable ADMET properties, including good oral bioavailability and moderate toxicity levels, suggesting their potential as candidates for drug development. However, certain compounds, such as cucurbitacin, dihydro, and gentesic acid exhibited potential toxicity, necessitating careful consideration in therapeutic applications. The integration of GC-MS with in-silico ADMET analysis provides a data of the pharmacological potential and safety of M. charantia ethanol extract, supporting its traditional use and encouraging further exploration as a source of bioactive compounds for pharmaceutical development.

Atherosclerosis is an inflammatory disease mediated by interferon (IFN-γ) in concert with cell adhesion molecules and chemokines. Thymoquinone (TQ), a flavonoid derived from Nigella sativa, is reported to have anti-inflammatory, antioxidant, and cardiovascular protective properties. We evaluated the effects of TQ on the key pathogenic stages of atherosclerosis, including cell viability, inflammatory gene expression, cell migration, and cholesterol efflux, on human THP-1 macrophages in-vitro. Moreover, in-silico analysis was performed to predict the molecular targets and signaling mechanisms. We demonstrated that TQ treatment had no effect on cell viability and decreased the expression of monocyte chemoattractant protein (MCP-1) and intercellular adhesion molecule (ICAM-1) in response to IFN-γ. In addition, we have also demonstrated that the THP-1 cell migration was inhibited by TQ in the absence or presence of MCP-1. Thymoquinone had no effect on cholesterol efflux from monocytes. In-silico analysis also identified several putative targets for TQ that are associated with inflammatory diseases and associated signaling pathways. Collectively, these results suggest that TQ has anti-inflammatory effects and may be a potential nutraceutical candidate for the prevention and treatment of atherosclerosis.

Heterocyclic compounds are that type of substances that are deeply intertwined with biological processes. Heterocycles are found in about 90% of commercially available medicines. In medicinal chemistry, finding new synthetic molecules with drug-like characteristics is a regular problem, which triggered the development of pharmacological molecules, the majority of which are based on N-heterocyclic motifs. Among the heterocycles, the pyrrole scaffold is the most commonly found heterocycle in both natural and synthetic bioactive compounds. Pyrrole has a fivemembered heterocyclic ring with a plethora of pharmacophores, resulting in a library of different lead compounds. Pyrrole derivatives are physiologically active heterocyclic compounds that can be used as scaffolds for antibacterial, antiviral, anticancer, antitubercular, anti-inflammatory, and as enzyme inhibitors. On account of their extensive pharmacological profile, pyrrole and its various synthetic derivatives have drawn much attention from researchers to explore it for the benefit of humankind. This review presents an overview of recent developments in the pyrrole derivatives against multiple therapeutic targets.

Teclea nobilis is a medicinal plant widely used to treat oral pathogens, gonorrhea, fever, analgesics, asthma, joint pains, pneumonia, and intestinal worms in Ethiopia. Anticipated by these claims, column chromatographic separation of the roots extract of T. nobilis led to the isolation of eight alkaloids (1-8). The structures of the isolated compounds were identified based on their NMR (1D and 2D) spectral data analysis and comparison with reported literature data. In-silico molecular docking analysis of the isolated compounds were performed against Staphylococcus aureus DNA Gyrase (PDB ID: 2XCT) and human topoisomerase IIβ DNA (PDB ID: 3QX3) by using AutoDock Vina. ADMET analysis were performed by SwissADME, PreADMET, and OSIRIS Property predictions. The study revealed that the isolated compounds exhibited promising binding affinity toDNA gyrase, especially with compound 5 forms a stable drug-protein complex. Whereas the ADME and drug-likeness analysis revealed that compound 5 is less absorbed from the gastrointestinal tract, crossblood brain barrier and a P-glycoprotein substrate. This indicated that compound 5 could be a good candidate as anticancer agent provided that in vivo analysis done for more confirmation.

Monocarbonyl curcumin-quinoline molecular hybrids: Synthesis, antibacterial, and antioxidant evaluation combined with in silico predictions

One of the major universal causes of death is Tuberculosis. Despite the well-defined Tuberculosis pharmaceutical procedures, the lengthier treatment, medication tolerance, and harmfulness make disease control challenging. The present research focuses on the PROA, a protein that is crucial for catalyzing the reduction of L-glutamate 5-phosphate into L-glutamate 5-semialdehyde and phosphate. Utilising computational techniques, the homology modelling of the PROA protein model is created and verified. The 415 amino acids, which make up the PROA protein are organised into 18 helices and 16 sheets. The CASTp, FT-Site, and GalaxyWeb servers are used to determine the PROA protein's active site. The potential sites are ALA30, ARG204, VAL265 and CYS266. To discover the lead compounds, Schrodinger runs virtual screening tests. The Prime MM-GBSA programme is used to refine the lead compounds. The ADME properties of the lead compounds are calculated to ascertain their drug-like characteristics.

The host dietary fibre is fermented into short-chain fatty acids (SCFA) by intestinal microbiota as bacterial metabolites like propionate, acetate and butyrate. Among these metabolites, the role of butyrate is well documented to provide energy to intestinal epithelial cells. Also, butyrate has anti-inflammatory and anti-tumour properties and decrease in its level by unbalanced diet can develops cancer. Lately, some research has suggested that sodium butyrate as an inhibitor of histone deacetylase (HDAC) may have anticancer potential for hepatocellular carcinoma (HCC), the most common type of liver cancer. Since, HCC is asymptomatic it is usually diagnosed at its advanced stage. Sorafenib with antiproliferative and antiangiogenic effects is the first line of treatment in advanced HCC. However, prolonged drug treatment to HCC patients develops adaptive resistance towards the sorafenib. Sorafenib resistance can also be enhanced by differentially expressed microRNAs. However, the significance of butyrate in HCC sorafenib resistance and its association with sorafenib-targeted microRNAs is yet to be unfurled. Here, an attempt has been made to explore the role of bacterial metabolite butyrate on sorafenib resistant HCC as well as on sorafenib-targeted microRNAs (miR-7641 and miR-199) to curtail sorafenib resistance in HCC. Initially, in-silico analysis was performed using Human Metabolome Database (HMDB) so to identify specific butyrate producing faecal bacteria. Then, their specific 16s rRNA expression was compared between HCC patients and healthy individuals using qRT-PCR. Additionally, the cell viability (MTT) and apoptosis assays were performed in both parental and sorafenib resistant HepG2 cells to evaluate the role of sodium butyrate in sorafenib resistant HCC. Moreover, the association of sodium butyrate with sorafenib-targeted miR-7641 and miR-199 was also assessed using real time PCR, cell viability, cell apoptosis and transfection assays. In silico analysis demonstrated Roseburia cecical, Roseburia intestinalis, Eubacterium rectal, Faecalibacterium prausnitzii as specific butyrate producing faecal bacteria and their 16s rRNA expression was downregulated in HCC patients. In vitro study revealed the presence of sodium butyrate also decreased the cell viability as well as enhanced cell apoptosis of both parental and resistant HepG2 cells. Interestingly, sodium butyrate also decreased the expression of both sorafenib-targeted miR-7641 and miR-199. Further, combination of both sodium butyrate and antimiR-7641 or antimiR-199 also increased apoptosis and decreased viability of resistant cells. This is first study to unravel the association of butyrate producing bacteria with HCC patients and the significance of bacterial metabolite butyrate as anti-tumour in sorafenib resistant hepatocellular carcinoma. The study also demonstrated the plausible new aspects of bacterial metabolite butyrate association with sorafenib-targeted miRNAs (miR-7641 and miR-199). Hence, the study highlighted the therapeutic potential of bacterial metabolite butyrate that might improve the clinical management of hepatocellular carcinoma.

Coxiella burnetii, the causative agent of Q fever, is an intracellular pathogen posing a significant global public health threat. There is a pressing need for dependable and effective treatments, alongside an urgency for further research into the molecular characterization of its genome. Within the genomic landscape of Coxiella burnetii, numerous hypothetical proteins remain unidentified, underscoring the necessity for in-depth study. In this study, we conducted comprehensive in silico analyses to identify and prioritize potential hypothetical protein of Coxiella burnetii, aiming to elucidate the structure and function of uncharacterized protein. Furthermore, we delved into the physicochemical properties, localization, and molecular dynamics and simulations, and assessed the primary, secondary, and tertiary structures employing a variety of bioinformatics tools. The in-silico analysis revealed that the uncharacterized protein contains a conserved Mth938-like domain, suggesting a role in preadipocyte differentiation and adipogenesis. Subcellular localization predictions indicated its presence in the cytoplasm, implicating a significant role in cellular processes. Virtual screening identified ligands with high binding affinities, suggesting the protein’s potential as a drug target against Q fever. Molecular dynamics simulations confirmed the stability of these complexes, indicating their therapeutic relevance. The findings provide a structural and functional overview of an uncharacterized protein from C. burnetii, implicating it in adipogenesis. This study underscores the power of in-silico approaches in uncovering the biological roles of uncharacterized proteins and facilitating the discovery of new therapeutic strategies. The findings provide valuable preliminary data for further investigation into the protein’s role in adipogenesis.

Achyranthes aspera and Cissus quadrangularis are important medicinal plants possessing wide biological activity. The natural products obtained from plants provides an unique opportunity for the development of new drugs but due to their complex nature there is a need to isolate and purify the bioactive compounds from plant extracts by separation techniques. Our earlier findings revealed that methanol extracts of A. aspera and C. quadrangularis and aqueous extract of C. quadrangularis exhibited antibacterial activity. This prompted to take up further research to reveal these plants’ potential valuable phytochemicals and therefore an attempt has been made to separate the phytochemical constituents of methanol and aqueous extracts of A. aspera and C. quadrangularis by thin layer chromatography. Phytochemical screening of both plant extracts revealed more concentrated phytochemicals in methanol extracts than in aqueous extracts. The TLC profiling showed that methanol extract of A. aspera and C. quadrangularis are rich in flavonoids and phenolic compounds. Flavonoids were separated with n-butanol:ethyl acetate:water (1:2:3) solvent system at Rf value of 0.66 and was confirmed by post-development derivatization with 3% boric acid and 10% oxalic acid spray. After derivatization, the flavonoid spot could be further visualized under UV light at 254nm. Phenolic compounds were separated with methanol:water (2:1) solvent system at Rf value of 0.88 and confirmed with 10% ferric chloride spray. From the present study, suitable mobile phase for separation of flavonoids and phenolic compound fraction from methanol and aqueous extracts of both plants and TLC profiling have been developed.

A novel series of N-pyrazolyl-thienopyrimidine and pyridopyrimidine hybrids was synthesized and characterized using spectroscopic methods. Compounds 4c, 5c, and 12 exhibited superior antibacterial potency compared to Levofloxacin, with molecular docking revealing strong binding to key bacterial targets (e.g., DNA gyrase, Neuraminidase). In-silico ADMET analysis confirmed favorable drug-like properties and low toxicity for 4c, supported by stable molecular dynamics interactions. Additionally, 5c and 12 demonstrated potent anti-inflammatory activity surpassing Celecoxib, with reduced ulcerogenicity. These findings introduce a promising new class of dual-action agents for antibacterial and anti-inflammatory drug development.

Pyridopyrimidine are heterocyclic molecules enclosing fused pyridine and pyrimidine rings. Owing to its fascinating core structure and pharmacological applications a series of 7-([1,1′-biphenyl]-4-yl)-5-arylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones were synthesized and characterized using IR, 1H, 13C NMR and Mass spectral techniques. The antibacterial, antioxidant and anticancer activities were investigated for the synthesized compound 5a-5f. Compounds with electron-donating groups showed excellent free radical scavenging activity. Halogen-substituted compounds showed more potent antimicrobial and anticancer activity than other derivatives in comparison with their respective standards. Based on the IC50 value obtained from anticancer activity, 5c was further analyzed for apoptosis by AO/EB staining method. The findings suggested early apoptosis in the MCF-7 cell line. Molecular Docking studies of the synthesized compounds were performed with Kinase 1 inhibitors (PDB id: 2YEX), 5c exposed good docking results with minimum binding energy. Further, these compounds were acknowledged as orally active drug candidates from in-silico ADMET studies. Computational analysis supports biological findings indicating compound 5c as a promising anticancer agent against the human breast cancer MCF-7 cell line.

In vivo and in silico assays demonstrate that the hydroalcoholic extract of Aloysia polystachya and carvone promote anti-ulcer effects.