Drug-like Characteristics Research Articles

Identification of natural inhibitors targeting Trehalase of Anopheles funestus in the management of malaria: A Biocomputational assessment.

Anopheles funestus is playing an increasingly important role in malaria transmission in sub-Saharan Africa. Trehalase, an enzyme required for trehalose breakdown, is important for mosquito flight and stress adaptation. Hence, its inhibition has emerged as a promising malaria management strategy. A collection of 1900 natural compounds from the ZINC database were screened against the 3D modeled structure of the A. funestus trehalase protein using in-silico tools. ADMET-AI, a web-based platform, was used to predict the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the selected compounds. Here in this study, we report 5 natural compounds namely, ZINC00488388, ZINC00488525, ZINC00488566, ZINC00488304, and ZINC00488456 demonstrated strong binding affinity to the trehalase protein. These compounds interacted with critical residues of the trehalase protein and exhibited good drug-like characteristics. These compounds show promise as trehalase protein inhibitors for malaria management. Nonetheless, additional experimental studies are required to optimize these compounds as potential trehalase inhibitors.

Identification of coumarin – benzimidazole hybrids as potential antibacterial agents: Synthesis, in vitro and in vivo biological assessment, and ADMET prediction

The direct-linked coumarin-benzimidazole hybrids, featuring aryl and n-butyl substituents at the N1-position of benzimidazole were synthesized through a Knoevenagel condensation reaction. This reaction involved the condensation of 1,2-diaminobenzene derivatives with coumarin-3-carboxylic acids in the presence of polyphosphoric acid (PPA) at 154 °C. The in vitro antibacterial potency of the hybrid molecules against different gram-positive and gram-negative bacterial strains led to the identification of the hybrids 6m and 6p with a MIC value of 6.25 μg/mL against a gram-negative bacterium, Klebsiella pneumonia ATCC 27736. Cell viability studies on THP-1 cells demonstrated that the compounds 6m and 6p were non-toxic at a concentration of 50 µM. Furthermore, in vivo efficacy studies using a murine neutropenic thigh infection model revealed that both compounds significantly reduced bacterial (Klebsiella pneumonia ATCC 27736) counts (more than 2 log) compared to the control group. Additionally, both compounds exhibited favorable physicochemical properties and drug-likeness characteristics. Consequently, these compounds hold promise as lead candidates for further development of effective antibacterial drugs.

Computational Insights into Chromene/pyran Derivatives: Molecular Docking, ADMET Studies, DFT Calculations, and MD Simulations as Promising Candidates for Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative condition characterized by both motor and non-motor symptoms. Although PD is commonly associated with a decline of dopaminergic neurons in the substantia nigra, other diagnostic criteria and biomarkers also exist. In the search for novel therapeutic agents, chromene and pyran derivatives have shown potential due to their diverse pharmacological activities. This study utilizes a comprehensive computational approach to investigate the viability of chromene/pyran compounds as potential treatments for PD. The drug-likeness characteristics of these molecules were analyzed using ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) studies. Molecular docking was performed against PDB ID: 2V5Z. The best three molecules chosen were compound 7, compound 24, and compound 67 have a binding energy of -6.7, -8.6, and -10.9 kcal/mol. Molecules demonstrating positive blood-brain barrier permeability, good solubility, and favorable binding affinity were further evaluated using Density Functional Theory (DFT) calculations and Molecular Dynamics (MD) simulations to assess their electronic structure and stability. DFT calculations indicated that molecule 82 has a dipole moment of 15.70 D. RMSD and RMSF results confirmed the stability of the complexes over a 100 ns simulation, with a maximum of 3 hydrogen bonds formed.

Deciphering the therapeutic actions of Brenania brieyi (Rubiaceae) fractions on oxidoinflammatory anomalies

A decline in the antioxidant network during the inflammatory response plays a critical role in the pathogenesis of numerous diseases. We designed this study to decipher the therapeutic efficacy of Brenania brieyi in reducing oxidative stress caused by the inflammatory response to cotton pellets. Graded doses of methanol and chloroform fractions of B. brieyi (MFBB and CFBB) and indomethacin were administered to Wistar rats for seven days after implanting sterilised cotton pellets (20 mg). Thereafter, biochemical indices of oxidative stress were determined using blood samples taken through cardiac puncture. Furthermore, molecular interactions, drug-likeness, and toxicity features of B. brieyi phytochemicals were also assessed. Compared with the untreated group, the groups treated with MFBB and CFBB had a significant (p < 0.05) decrease in granuloma tissue weight and MDA levels while increasing glutathione levels, SOD, and CAT activities. In addition, a substantial increase in inflammatory-induced changes in antioxidant nutrients, together with a decline in liver enzymes, was obtained in the treated groups. The docking tests revealed that the top-scoring phytoconstituents of B. brieyi, n-hexadecanoic acid, and 9-octadecanoic acid interacted well with catalase, having docking scores of -6.19 and -7.58 kcal/mol, respectively. Moreover, the hits had good oral drug-likeness features and a safe toxicity profile. The findings of the study provide evidence that B. brieyi has antioxidant and anti-inflammatory properties, suggesting that it could be used as an alternative therapy to regulate oxidative stress-related diseases.

Discovery and prospects of new heterocyclic Isatin-hydrazide derivative with a novel role as estrogen receptor α degrader in breast cancer cells.

Introduction: Isatin, a heterocycle scaffold, is the backbone of many anticancer drugs and has previously been reported to engage multiple cellular targets and mechanisms, including angiogenesis, cell cycle, checkpoint pathways and multiple kinases. Here, we report that a novel isatin derivative, 5i, degrades estrogen receptor alpha (ERα) in estrogen-dependent breast cancer cells. This effect of the isatin nucleus has not been previously reported. Tamoxifen and fulvestrant represent standard therapy options in estrogen-mediated disease but have their own limitations. Isatin-based triple angiokinase inhibitor BIBF1120 (Nintedanib) and multikinase inhibitor Sunitinib (Sutent) have been approved by the FDA. Methods: Keeping this in view, we synthesized a series of N'-(1-benzyl-2-oxo-1, 2-dihydro-3H-indol-3-ylidene) hydrazide derivatives and evaluated them in vitro for antiproliferative activities in MCF-7 (ER+) cell line. We further investigated the effect of the most potent compound (5i) on the Erα through Western Blot Analysis. We used in silico pharmacokinetics prediction tools, particularly pkCSM tool, to assess the activity profiles of the compounds. Results and discussion: Compound 5i showed the best antiproliferative activity (IC50 value; 9.29 ± 0.97µM) in these cells. Furthermore, 5i downregulated ERα protein levels in a dose-dependent manner in MCF-7. A multifaceted analysis of physicochemical properties through Data Warrior software revealed some prominent drug-like features of the synthesized compounds. The docking studies predicted the binding of ligands (compounds) with the target protein (ERα). Finally, molecular dynamics (MD) simulations indicated stable behavior of the protein-ligand complex between ERα and its ligand 5i. Overall, these results suggest that the new isatin derivative 5i holds promise as a new ERα degrader.

Synthesis, quantum chemical calculations, in silico and in vitro bioactivity of a sulfonamide-Schiff base derivative

The sulfonamide Schiff base compound (E)-4-((4-(dimethylamino)benzylidene)amino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide was successfully prepared and fully characterized. The foremost objective of this study was to explore the molecular geometry of the aforementioned compound and determine its drug likeness characteristics, docking ability as an insulysin inhibitor, anticancer and antioxidant activities. The molecular structure of this compound was optimized using the B3LYP/6−311G+(d,p) level of theory. The compound was completely characterized utilizing both experimental and DFT approaches. Molecular electrostatic potential, frontier molecular orbitals, Fukui function, drug likeness, and in silico molecular docking analyses of this compound were performed. Wave functional properties such as localized orbital locator, electron localization function and non-covalent interactions were also simulated. The compound was screened for anticancer and antioxidant activities using in vitro technique. The observed FT-IR, UV–Vis, and 1H NMR results compared with simulated data and both results were fairly consistent. The experimental and computational spectral findings confirm the formation of the Schiff base compound. Both π—π* and n—π* transitions were observed in both experimental and computational UV–Vis spectra. The examined compound followed to Pfizer, Golden Triangle, GSK, and Lipinski's rules. Consequently, it possesses a more favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile, making it a suitable candidate for non-toxic oral drug use. Moreover, the compound exhibited promising insulysin inhibition activity in an in silico molecular docking. The compound showed in vitro anticancer activity against A549 cancer cells with an IC50 value of 40.89 μg/mL and moderate antioxidant activity.

Inhibition of the Janus kinase protein (JAK1) by the A. Pyrethrum Root Extract for the treatment of Vitiligo pathology. Design, Molecular Docking, ADME-Tox, MD Simulation, and in-silico investigation

This study delves into the therapeutic efficacy of A. pyrethrum in addressing vitiligo, a chronic inflammatory disorder known for inducing psychological distress and elevating susceptibility to autoimmune diseases. Notably, JAK inhibitors have emerged as promising candidates for treating immune dermatoses, including vitiligo. Our investigation primarily focuses on the anti-vitiligo potential of A. pyrethrum root extract, specifically targeting N-alkyl-amides, utilizing computational methodologies. Density Functional Theory (DFT) is deployed to meticulously scrutinize molecular properties, while comprehensive evaluations of ADME-Tox properties for each molecule contribute to a nuanced understanding of their therapeutic viability, showcasing remarkable drug-like characteristics. Molecular docking analysis probes ligand interactions with pivotal site JAK1, with all compounds demonstrating significant interactions; notably, molecule 6 exhibits the most interactions with crucial inhibition residues. Molecular dynamics simulations over 500ns further validate the importance and sustainability of these interactions observed in molecular docking, favoring energetically both molecules 6 and 1; however, in terms of stability, the complex with molecule 6 outperforms others. DFT analyses elucidate the distribution of electron-rich oxygen atoms and electron-poor regions within heteroatoms-linked hydrogens. Remarkably, N-alkyl-amides extracted from A. pyrethrum roots exhibit similar compositions, yielding comparable DFT and Electrostatic Potential (ESP) results with subtle distinctions. These findings underscore the considerable potential of A. pyrethrum root extracts as a natural remedy for vitiligo.

BIOLOGICAL ACTIVITY OF ISOPROPYLAMINE ANTHRAQUINONE

The aim of the work. To predict the drug-likeness and toxicity using modern web tools of the isopropylaminoanthraquinone compound, as well as to experimentally prove a possible mechanism of antitumor activity. Materials and Methods. For the anthraquinone compound, an in silico drug-likeness and toxicity screening was performed using SwissADME and ProTox II online services. Prediction of the antitumor activity mechanism was analyzed using the US National Cancer Institute (NCI) PRISM service. Results and Discussion. 1-Amino-4-(isopropylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic acid was synthesized by the reaction of nucleophilic substitution of bromamic acid with isopropylamine, which acted as a nucleoforming agent. The structure of the synthesized derivative (98% yield) was confirmed by 1H, 13C NMR, IR and LC-MS spectra. The studied anthraquinone compound showed satisfactory drug-like characteristics and a low toxicity profile. Conclusions. The obtained results may become a platform for further structural optimization of the identified compound based on anthraquinone with an isopropylamine fragment in the development of modern anticancer drugs.

A series of pyrimidine-based antifungals with anti-mold activity disrupt ER function in Aspergillus fumigatus.

Fungal infections are a major contributor to morbidity and mortality among immunocompromised populations. Moreover, fungal disease caused by molds are difficult to treat and are associated with particularly high mortality. To address the need for new mold-active antifungal drugs, we performed a high-throughput screen with Aspergillus fumigatus, the most common pathogenic mold. We identified a novel, pyrimidine-based chemical scaffold with broad-spectrum antifungal activity including activity against several difficult-to-treat molds. A chemical genetics screen of Saccharomyces cerevisiae suggested that this compound may target the endoplasmic reticulum (ER) and perturb ER function and/or homeostasis. Consistent with this model, this compound induces the unfolded protein response and inhibits secretion of A. fumigatus collagenases. Initial cytotoxicity and pharmacokinetic studies show favorable features including limited mammalian cell toxicity and bioavailability in vivo. Together, these data support the further medicinal chemistry and pre-clinical development of this pyrimidine scaffold toward more effective treatments for life-threatening invasive mold infections.IMPORTANCEInvasive fungal diseases are life-threatening infections caused by fungi in immunocompromised individuals. Currently, there are only three major classes of antifungal drugs available to treat fungal infections; however, these options are becoming even more limited with the global emergence of antifungal drug resistance. To address the need for new antifungal therapies, we performed a screen of chemical compounds and identified a novel molecule with antifungal activity. Initial characterization of this compound shows drug-like features and broad-spectrum activity against medically important fungi. Together, our results support the continued development of this compound as a potential future therapy for these devastating fungal infections.

<i>In silico</i> evaluation of hypericin and pseudohypericin as candidates for monkeypox treatment

Monkeypox (Mpox) is a viral zoonotic and human-to-human disease with no specific drug or treatment protocol targeting the monkeypox virus (MPXV). In the MPXV life cycle, viral kinase phosphorylation plays a crucial role in early morphogenesis in the cytoplasm, making inhibition of MPXV kinase a potential therapeutic approach for controlling Mpox. Hypericum sampsonii contains several bioactive compounds, such as hypericin and pseudohypericin, which are known for their antiviral properties. In this study, a computational investigation of the physicochemical properties of hypericin and pseudohypericin revealed drug-like characteristics. Pharmacokinetic predictions indicated that hypericin and pseudohypericin are non-toxic to the central nervous system, hepatic system, and cardiac system. Molecular docking results indicated a strong binding affinity of hypericin/pseudohypericin with MPXV thymidylate kinase. As a result, these compounds are being considered as potential Mpox control candidates.

Machine learning-based QSAR and LB-PaCS-MD guided design of SARS-CoV-2 main protease inhibitors

The global outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 virus had led to profound respiratory health implications. This study focused on designing organoselenium-based inhibitors targeting the SARS-CoV-2 main protease (Mpro). The ligand-binding pathway sampling method based on parallel cascade selection molecular dynamics (LB-PaCS-MD) simulations was employed to elucidate plausible paths and conformations of ebselen, a synthetic organoselenium drug, within the Mpro catalytic site. Ebselen effectively engaged the active site, adopting proximity to H41 and interacting through the benzoisoselenazole ring in a π-π T-shaped arrangement, with an additional π-sulfur interaction with C145. In addition, the ligand-based drug design using the QSAR with GFA-MLR, RF, and ANN models were employed for biological activity prediction. The QSAR-ANN model showed robust statistical performance, with an r2training exceeding 0.98 and an RMSEtest of 0.21, indicating its suitability for predicting biological activities. Integration the ANN model with the LB-PaCS-MD insights enabled the rational design of novel compounds anchored in the ebselen core structure, identifying promising candidates with favorable predicted IC50 values. The designed compounds exhibited suitable drug-like characteristics and adopted an active conformation similar to ebselen, inhibiting Mpro function. These findings represent a synergistic approach merging ligand and structure-based drug design; with the potential to guide experimental synthesis and enzyme assay testing.

In silico screening of Fyn kinase inhibitors using classification-based QSAR model, molecular docking, molecular dynamics and ADME study.

This study aimed to use a computational approach that combined the classification-based QSAR model, molecular docking, ADME studies, and molecular dynamics (MD) to identify potential inhibitors of Fyn kinase. First, a robust classification model was developed from a dataset of 1,078 compounds with known Fyn kinase inhibitory activity, using the XGBoost algorithm. After that, molecular docking was performed between potential compounds identified from the QSAR model and Fyn kinase to assess their binding strengths and key interactions, followed by MD simulations. ADME studies were additionally conducted to preliminarily evaluate the pharmacokinetics and drug-like characteristics of these compounds. The results showed that our obtained model exhibited good predictive performance with an accuracy of 0.95 on the test set, affirming its reliability in identifying potent Fyn kinase inhibitors. Through the application of this model in conjunction with molecular docking and ADME studies, nine compounds were identified as potential Fyn kinase inhibitors, including 208 (ZINC70708110), 728 (ZINC8792432), 734 (ZINC8792187), 736 (ZINC8792350), 738 (ZINC8792286), 739 (ZINC8792309), 817 (ZINC33901069), 852 (ZINC20759145), and 1227 (ZINC100006936). MD simulations further demonstrated that the four most promising compounds, 728, 734, 736, and 852 exhibited stable binding with Fyn kinase during the simulation process. Additionally, a web-based platform ( https://fynkinase.streamlit.app/ ) has been developed to streamline the screening process. This platform enables users to predict the activity of their substances of interest on Fyn kinase from their SMILES, using our classification-based QSAR model and molecular docking.

In silico investigation and biological evaluation viz antimicrobial, genotoxic, and anticancer potentials of new dihydropyrimidinones (DHPMs) synthesized by Biginelli reaction

Dihydropyrimidin-2(1H)-ones (DHPMs) are attracting growing interest in synthetic and medical organic chemistry due to their biological and therapeutic potential. In this study, we synthesized DHPM derivatives via the Biginelli reaction from bisdialdehyde to identify lead compounds. Using SWISSADME analysis, we assessed druglikeness features of the DHPM derivatives. Antimicrobial properties, including antibacterial and antifungal activities, were evaluated, and promising compounds were tested for their ability to inhibit A549 lung cancer cell growth. Thin-layer chromatography confirmed product formation, while spectroscopic methods characterized the structures. Lipophilicity values indicated strong oral absorption potential. In vitro drug release and cell viability studies were conducted. DHPMs 7, 8, and B1 exhibited broad-spectrum antimicrobial activity. Molecular docking revealed DHPM 2′s potential in cancer treatment via effective binding with VEGFR-2 kinase. Genotoxic and anticancer activities were assessed, with DHPM 8 showing promising action against dangerous bacteria and fungi. Further research is warranted to explore therapeutic applications of these compounds.

In silico and in vitro study of bioactive compounds from Allium sativum with PTEN: A novel target and promising source for cancer diagnostic potentials

IntroductionCancer remains a significant global health issue, necessitating innovative management strategies. The tumor suppressor protein PTEN, due to its pivotal role in cancer development, is a promising target for therapeutic intervention. Materials and MethodsWe used dried Allium sativum (garlic) seed extract to discover phytocompounds that could inhibit PTEN in cancer. We conducted qualitative tests to determine the phytochemical composition of the extract and employed a DPPH radical scavenging assay to evaluate its antioxidant activity. Computational methods were used to explore the impact of Allium sativum and its constituents on PTEN. This involved predicting and validating 3D structures using the SWISS model and ITASSER, performing docking analysis with natural compounds from the Asinex database, and assessing the drug-likeness and ADMET characteristics of selected compounds using online tools. Molecular dynamics simulations (MDS) were conducted to examine protein–ligand interactions, and the results were analyzed to understand complex stability and fluctuations. ResultsA study on Allium sativum revealed the presence of diverse phytochemicals in its seeds and leaves. The leaves contained alkaloids and saponins, while the methanol extract of the leaves exhibited the highest flavonoid and phenolic contents. This methanol extract demonstrated potent antioxidant activity and significantly inhibited cytotoxicity. Through computer-aided drug design, we identified potential anticancer drugs derived from natural botanicals that target the PTEN protein. The virtual screening process led to the discovery of three lead compounds exhibiting high binding affinities and interactions with PTEN. Molecular docking and MDS indicated the strong binding energy and favorable drug-like properties of these compounds. While the protein exhibited some flexibility, the ligand–protein complex remained stable. ConclusionThis study contributes to the expanding literature on cancer drug discovery and emphasizes the importance of investigating natural plant compounds in the search for novel and effective cancer treatments.

Exploring the therapeutic mechanisms of Astonia boonei in diabetes mellitus ligand-based virtual screening with TGR5 Receptor

The anti-diabetic effects of Astonia boonei have been demonstrated by several studies, but few have clarified the mode of action of compounds extracted from Astonia boonei as an agonist for the TGR5 pathways in the etiology of diabetes. TGR5 is a membrane protein receptor that has been linked to increased insulin-signaling and is an appropriate target for diabetes treatment. Nevertheless, no commercial medication that specifically targets TGR5 is currently available. This study looked into compounds that were found to be TGR5 agonists and may have therapeutic value in A. boonei. The compounds were selected from the literature and docked with TGR5 receptors. Following their filtration by Lipinski's rule of five (RO5), the compounds were utilized in a molecular docking investigation. Moderate indices for ADMET parameters and non-carcinogenicity were revealed by online web servers' predictions of the hit compounds' drug-likeness, pharmacokinetic, and toxicity features. The potential of compounds from A. boonei that might be explored as therapeutic options in the treatment of diabetes is thus illuminated by this study

Identification of TonB-dependent siderophore receptor inhibitors against Flavobacterium columnare using a structure-based high-throughput virtual screening method.

TonB-dependent siderophore receptors play a critical transport role for Flavobacterium columnare virulence formation and growth, and have become valuable targets for the development of novel antimicrobial agents. Traditional Chinese medicine has demonstrated notable efficacy in the treatment of fish diseases and includes potential antibacterial agents. Herein, we performed molecular docking-based virtual screening to discover novel TonB-dependent siderophore receptor inhibitors from traditional Chinese medicine and provide information for developing novel antibacterial agents. Firstly, we efficiently obtained 11 potential inhibitors with desirable drug-like characteristics from thousands of compounds in the TCM library based on virtual screening and property prediction. The antibacterial activity of Enoxolone, along with its interaction characteristics, were determined via an MIC assay and molecular dynamic simulation. Transcriptional profiling, along with validation experiments, subsequently revealed that an insufficient uptake of iron ions by bacteria upon binding to the TonB-dependent siderophore receptors is the antibacterial mechanism of Enoxolone. Finally, Enoxolone's acceptable toxicity was illustrated through immersion experiments. In summary, we have used virtual screening techniques for the first time in the development of antimicrobial agents in aquaculture. Through this process, we have identified Enoxolone as a promising compound targeting the TonB-dependent siderophore receptor of F. columnare. In addition, our findings will provide new ideas for the advancement of innovative antimicrobial medications in aquaculture.

Novel esters derived from 4-hydroxychalcones as potential sunscreens with antimicrobial action

Ten novel 4-esterchalcones, licochalcone analogues, were strategically synthesized to study the effect of electro-donating or electro-withdrawing substituents in the aryl enone moiety on their pharmacological and photoprotective properties. 4-Esterchalcones had their drug-like character evaluated, which demonstrated positive characteristics for the development of novel drug candidates. In the in vitro antimicrobial evaluation, isovaleryl 4-esterchalcones showed activity against strains of Staphylococcus aureus, Candida albicans and C. tropicalis with minimum inhibitory concentration (MIC) in the range of 2.64-3.32 µmol mL−1, and the isobutyryl 4-esterchalcone 5d (4’-Br) presented antimicrobial activity against all strains tested, with a MIC of 2.74 µmol mL−1. In the UV-Vis study, λ max were observed at 312-327 nm, the UVB range, mainly. The best SPF-UVB results ranged from 18.04 to 21.06, with high ε max values, indicating that 4-esterchalcones have the potential to act as sunscreens. Furthermore, along with the environmental concern, halogenated compounds demonstrated slightly toxic on Artemia salina.

Structure-based design of multitargeting ChEs-MAO B inhibitors based on phenyl ring bioisosteres: AChE/BChE selectivity switch and drug-like characterization

A structure-based drug design approach was focused on incorporating phenyl ring heterocyclic bioisosteres into coumarin derivative 1, previously reported as potent dual AChE-MAO B inhibitor, with the aim of improving drug-like features. Structure-activity relationships highlighted that bioisosteric rings were tolerated by hMAO B enzymatic cleft more than hAChE. Interestingly, linker homologation at the basic nitrogen enabled selectivity to switch from hAChE to hBChE. In the present work, we identified thiophene-based isosteres 7 and 15 as dual AChE-MAO B (IC50 = 261 and 15 nM, respectively) and BChE-MAO B (IC50 = 375 and 20 nM, respectively) inhibitors, respectively. Both 7 and 15 were moderately water-soluble and membrane-permeant agents by passive diffusion (PAMPA-HDM). Moreover, they were able to counteract oxidative damage induced by both H2O2 and 6-OHDA in SH-SY5Y cells and predicted to penetrate into CNS in a cell-based model mimicking blood-brain barrier. Molecular dynamics (MD) simulations shed light on key differences in AChE and BChE recognition processes promoted by the basic chain homologation from 7 to 15.

Exploring the spectral and nonlinear optical properties of phenyl isothiocyanate through density functional theory and molecular docking studies: A comprehensive analysis of a potent biologically active phytochemical

Quantum chemical calculations employing Density Functional Theory (DFT) with 6–31G (d,p) basis sets have yielded valuable insights into the molecular structure, Frontier Molecular Orbitals (FMOs), Mulliken Charges, and Molecular Electrostatic Potential Maps of the phenyl isothiocyanate (PITC) molecule. Spectral analysis of PITC has been conducted including Fourier transform infrared (FTIR), Fourier transform Raman (FT-RAMAN), Nuclear Magnetic Resonance (NMR), and ultraviolet–visible (UV–Vis) spectroscopy by theoretical method. Additionally, global descriptive parameters and thermal properties have also been determined. The Nonlinear Optical characteristic (NLO) has been assessed in the gas phase using the same level of theory. The investigation into toxicity revealed that the studied molecule exhibits drug-like characteristics and is non-toxic. Molecular docking studies have been employed to investigate hydrogen bond interactions, elucidating the minimal binding energy of the compound. The outcomes of the docking studies strongly suggest the significant biological activity of Phenyl Isothiocyanate, emphasizing its potential as a potent phytochemical.

ADME/PK Insights of Crocetin: A Molecule Having an Unusual Chemical Structure with Druglike Features.

Crocetin is a promising phyto-based molecule to treat Alzheimer's disease (AD). The chemical structure of crocetin is incongruent with various standard structural features of CNS drugs. As poor pharmacokinetic behavior is the major hurdle for any candidate to become a drug, we elucidated its druggable characteristics by implementing in silico, in vitro, and in vivo approaches, as limited ADME/PK information is available. Results demonstrate several attributes of crocetin based on rules of drug-likeness, lipophilicity, pKa, P-gp inhibitory activity, plasma stability, RBC partitioning, metabolic stability, CYP inhibitory action, blood-brain barrier (BBB) permeability, oral bioavailability, and pharmacokinetic interaction with marketed anti-Alzheimer's drugs (memantine, donepezil, galantamine, and rivastigmine). However, aqueous solubility, chemical stability, plasma protein binding, and P-gp induction are some concerns associated with this molecule that should be taken into consideration during its further development. Overall results indicate favorable ADME/PK behavior and potential druggable candidature of crocetin.