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The growing focus on sustainable use of natural resources has brought attention to cashew nut shell liquid (CNSL), a by-product rich in anacardic acids (AAs) with potential applications in diabetes treatment. In this study, three different AAs from CNSL, monoene (15:1, AAn1), diene (15:2, AAn2), and triene (15:3, AAn3), and a mixture of the three (mix) were evaluated as α-glucosidase inhibitors. The samples were characterized by combining 1D and 2D NMR spectroscopy, along with ESI-MS. In vitro assays revealed that AAn1 had the strongest inhibitory effect (IC50 = 1.78 ± 0.08 μg mL−1), followed by AAn2 (1.99 ± 0.76 μg mL−1), AAn3 (3.31 ± 0.03 μg mL−1), and the mixture (3.72 ± 2.11 μg mL−1). All AAs significantly outperformed acarbose (IC50 = 169.3 μg mL−1). In silico docking suggested that polar groups on the aromatic ring are key for enzyme–ligand binding. The double bond at C15, while not essential, enhanced the inhibitory effects. Toxicity predictions classified AAs as category IV, and pharmacokinetic analysis suggested moderately favorable drug-like properties. These findings highlight AAs as a promising option in the search for new hypoglycemic compounds. [ABSTRACT FROM AUTHOR]

COX (Cyclooxygenase) is the protein that imparts the degradation of PG (prostaglandins) from its substrate, AA (arachidonic acid). Quinoline is an admirable group of various bioactive substances and a hydroxy (-OH) group attached to one of the carbon atom known as Hydroxyquinoline. Due to the diversified biological activity of the quinoline ring interest has been increased in developing new bioactive moieties of the same nucleus.I n this present work, we intend to study the interaction of fifteen hydroxyquinoline derivatives against COX-2 (1CX2) enzyme for anti-inflammatory activity using molecular docking simulation carried out by virtual Swissdock freeware to predict the degree of each COX binding pocket. For the prediction of their binding modes, the scoring function, hydrogen bonding, their binding affinities, and orientation of these compounds at the active site of the enzyme were used. The computational studies are also used to predict absorption, distribution, metabolism, elimination, toxicity, and the pharmacokinetic profile of some hydroxyl quinoline analogs. The investigated analogue possesses GI absorption and some compound has good BBB permeability. The side effects during the investigations are Mutagenicity, Hepatotoxicity, etc. [ABSTRACT FROM AUTHOR]

In this study, six compounds were obtained from a methanolic extract of air-dried leaves of Senna alata and one of them, a triterpenoid (secofriedelane) named as 7-(2-carboxyethyl)-3, 4b, 6a, 8, 10a, 12a-hexamethyl-8-vinyloctadecahydrochrysene-3-carboxylic acid (5) was isolated for the first time from this plant. Then, its chemical structure was detailed and characterised by FT-IR, 1H and 13C- NMR and ESI-MS. Besides, two chemical-modified derivatives of secofriedelane (5a, 5b) were synthesised by methylation and allylation reactions, respectively, and their in vitro antibacterial activities were also evaluated. The results revealed that all the triterpenes showed, against gram-positive and -negative bacterial strains, good and moderate antibacterial activities with bactericidal effects that were enhanced by the methyl groups and altered with the allyl ones. Moreover, the molecular docking results of 5, 5a and 5b in the DNA gyrase (2XCT) active site showed that triterpene 5 has a good score very close to reference (ciprofloxacin). [ABSTRACT FROM AUTHOR]

An efficient synthesis of a novel compound of hydrazine carbodithioate derivative of piperidone, (E)-methyl-2-(3-methyl-2,6-diphenylpiperidin-4-ylidene)hydrazinecarbodithioate (1), was performed using methyl dithiocarbazinate and 3-methyl-2,6-diphenylpiperidin-4-one as the starting materials. The reaction was carried out in an acidic medium using methanol as a solvent. The novel compound was characterized by FTIR, Mass, and NMR spectral techniques. The hydrazine carbodithioate derivative (1) was then tested for its anticancer activity against the liver cancer cell line, Hep G2, using the MTT assay. The IC50 values of the newly synthesized compound were found to be 34.33 ± 0.79 μM (24 hours) and 27.64 ± 1.42 μM (48 hours). The in vitro antitumor studies demonstrated that the novel compound (1) exhibited good inhibitory activity against the Hep G2 cancer cells. Furthermore, in silico properties such as lipophilicity, water solubility, pharmacokinetic properties, drug likeness, and medicinal chemistry were analyzed using the SwissADME tool. [ABSTRACT FROM AUTHOR]

In this article, we used thiophene-2-carboxamides as a starting material to synthesize a novel series of L-phenylalanine-tethered peptide hydrazones 6a–6o in three steps. The Broth Dilution Method was used to test the substance' s antibacterial activity in vitro against a variety of bacteria and fungi. Compounds 6c, 6d, and 6g showed potent antibacterial activity against E. coli (MTCC 443) at 50 µg/mL; compounds 6a, 6b, 6g, and 6l were effective against P. aeruginosa (MTCC 1688); compound 6c was effective against S. aureus (MTCC 96); and compound 6a, 6c, and 6g were effective against S. pyogenes (MTCC 442). 6a, 6b, 6d, 6e, 6f, 6h–6l, 6n, and 6o all show considerable antifungal activity against C. albicans (MTCC 227) at 500 µg/mL. The effectiveness of synthesized compounds in a microbiological study was predicted using an in silico investigation of their pharmacokinetic properties (ADME). [ABSTRACT FROM AUTHOR]

This study comprehensively analyzes molecular properties for neutral and protonated forms of adenine, caffeine, guanine, paraxanthine, theobromine, and theophylline. It highlights their shared bicyclic structures and biological relevance. Hirshfeld surface analysis reveals intricate interactions within the molecules, with color-coded regions indicating levels of proximity and potential hydrogen bonding. Noncovalent interactions and reduced density gradient analysis further elucidate the nature of interactions, encompassing van der Waals, steric, and hydrogen bonding. Topological parameters, examined through atom in molecule (AIM) analysis, emphasize the strength of hydrogen bonding within the molecules. Drug-likeness assessment underscores the compounds' alignment with drug-like attributes, driven by hydrogen bond donors, acceptors, and molecular weight. Natural bond order (NBO) analysis uncovers electron delocalization, bond order, and hybridization, elucidating interactions and stabilization energies. Nonlinear optical properties (NLO) analysis explores the potential for nonlinear optical phenomena, encompassing static dipole moment, polarizability, and hyper polarizability. The study delves into molecular orbitals and quantum chemical parameters, revealing insights into reactivity, electronegativity, ionization potential, and more. Protonation consistently influences these parameters, leading to shifts in energy levels, electronegativity, and reactivity. Collectively, this study provides a comprehensive understanding of molecular properties and interactions, offering valuable insights for potential applications and further research endeavors. [ABSTRACT FROM AUTHOR]

Diospyros batokana (Ebenaceae) is a valuable medicinal plant that grows in the wild in Zambia. The aqua crude plant extract is valuable in treating oxidative stress and microbes-related diseases. In this study, bioactive metabolites from the leaf of the plant were tentatively identified using ultra-high-pressure liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS). Raw LCMS data were processed using MZmine3.6. Pyrenophorol, N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl]-2,2-diphenylacetamide, losartan, and isoarthonin, (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide were among the many metabolites identified from the plant studied using LCMS-MZmine 3.6. Furthermore, in silico anti-inflammatory molecular docking was applied to the five (5) metabolites with the aim of predicting the ability of the metabolites to inhibit the COX-2 enzyme. The docking simulation for the five metabolites was executed using the Auto-dock tools. The lowest binding energy of the complexes was visualized using Discovery Studio, 2021 Client l molecular viewer. Pyrenophorol, (N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl] −2,2-diphenylacetamide) and losartan were found to provide the lowest binding energy to COX-2 compared to the standard anti-inflammatory drug, diclofenac. Furthermore, binding affinities, inhibition constants, and ligand efficiencies demonstrated that pyrenophorol, N-[1-(diethylamino)-3-morpholin-4-ylpropan-2-yl]-2,2-diphenylacetamide, losartan, isoarthonin and (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide could be useful as anti-inflammatory drug candidates supporting the traditional uses of D. batokana. However, the bioavailability radar and physicochemical properties only predict losartan, pyrenophorol, and (2E,4E)-N-[2-(4-hydroxyphenyl)ethyl]dodeca-2,4-dienamide to be bioavailable and suitable drug candidates. In silico and ADMET analysis, shows that the five metabolites could be used as anti-inflammatory drugs comparable to the standard drugs, diclofenac and ibuprofen. However, in vitro and in vivo studies are needed to further support our findings.

A panel of 1,1-(phenylene)bis[3-chloro-4-(substituted phenyl)azetidin-2-ones] (4a-m) and 3,3′-(1,4-phenylene)bis[2-(substituted phenyl)thiazolidin-4-ones] (5a-m) were synthesized from Schiff base intermediates 3a-m, that were in turn prepared from reaction between p-phenylenediamine and substituted benzaldehydes. The structures of title compounds and intermediates were confirmed by IR, 1H NMR, 13C NMR and mass spectral data. The compounds were screened for antibacterial, DPPH radical scavenging and antidiabetic activities. Compounds 4f and 4a exhibited good antibacterial activity against Gram-positive bacteria, but none showed appreciable activity against Gram-negative bacteria. In DPPH scavenging assay, compounds 5f, 5e and 5a exhibited good activity. Compound 5a displayed highly significant antidiabetic activity in fructose-induced diabetes in rats. The molecular docking studies of bis-thiazolidinones with PPAR-ã revealed the fit with high binding affinity and good interactions. Docking of compound 5a was comparable to the standard drug pioglitazone. The in silico physicochemical, drug-likeness and ADME properties of title compounds were also performed and the majority of them displayed satisfactory results. [ABSTRACT FROM AUTHOR]

The present study explored the potential of Byttneria herbacea Roxb. against inflammatory disease by conducting molecular docking studies. The SwissADME tool was utilized to perform a drug-likeness study, which was then followed by molecular docking using the AutoDock 4.2 software. In silico, GC-MS research identified 21 molecules, subsequently evaluated for drug-likeness properties. Based on the ADME analysis, six compounds were recognized as superior compounds. The docking analysis of these six molecules was performed with Autodock 4.2. Finally, two compounds were shown to be effective against Cyclooxygenase-2: 7-Methoxy-2,2-dimethyl2H-1-benzothiopyran and 3-buten-2-one, 4-(5,5-dimethyl-1-oxaspiro[2.5]oct-4-yl) against the enzyme (COX-1). Excellent docking properties and the lowest binding energy (-6.94 and -6.90 kcal/mol) were also found. According to the data, B. herbacea aerial plant component showed a significant anti-inflammatory molecular docking effect. [ABSTRACT FROM AUTHOR]

Cucurbitacin E (CuE) is a potent bioactive compound derived from the family of cucurbitaceae. CuE has recently been demonstrated to have outstanding potential to inhibit the growth of different kinds of cancer cells. CuE has been proven to have a strong anticancer effect on lung cancer in different in vitro and in vivo studies up to this date. In the present study, molecular docking of CuE was performed against three major proteins respectively myosin 9b [5C5S (Chain: A, B, C, D)], epidermal growth factor receptor (EGFRK) [1M17 (Chain: A)] and yes-associated protein (YAP) [3KYS (Chain: A, C)] associated with lung cancer. Different types of computers based softwires like GaussView 6.0, Gabedit, Swiss-PDB, Pymol, PyRx (Version 0.8), Discover Studio (2021) etc. are used for computational study. On the other hand, for developing the pharmacokinetic profile of the drug several online servers like Drug bank online, Pub Chem, RCSB:PDB, Webmo server, Online smile convertor, ADMET prediction, PASS prediction, Drug likeness analysis etc. are used. The molecular docking results showed that CuE possessed the best ligand protein interaction with 5C5S (Chain: A) protein where the binding score was -9.1 kJ/mol. Moreover, the non-bonding interactions ensure the significant binding affinity of CuE with 5C5S (Chain: A) protein to show antineoplastic effect against lung cancer. However, the present study reveals that CuE is the potent anti-lung cancer lead compound confirmed by the ligand protein interactions, ADMET calculation, PASS prediction and drug likeness analysis. Therefore, this study may be helpful towards the research community to think CuE as the best antineoplastic agent for treating lung cancer. [ABSTRACT FROM AUTHOR]

المخلص: أهداف البحث: كيناز ''ب.ر.أ. ف-في. 600.إي''. هو هدف علاجي أساسي في سرطان الجلد وأنواع أخرى من الأورام. تستلزم مقاومته للمثبطات والآثار الجانبية المعروفة لبعض المثبطات المحددة الاستقصاء عن مثبطات جديدة وفعالة. طرق البحث: في العمل الحالي، تم استخدام استراتيجيات في السيليكون مثل محاكاة الالتحام الجزيئي وتقييم الحرائك الدوائية وحسابات نظرية الكثافة الوظيفية لتحديد مثبطات ''ب.ر.أ. ف-في. 600.إي'' المحتملة من مجموعة من 72 مركبا مضادا للسرطان من قاعدة بيانات ''بوبكيم''. النتائج: ما مجموعه خمسة جزيئات من الدرجة الأولى (12 ، 15 ، 30 ، 31 ، 35) مع درجات رائعة في الالتحام (درجة مولدوك:> 90 كيلو كالوري مول -1 ، ونقاط إعادة التصنيف:> 60 كيلو كالوري مول -1) تم اختيارها. تم اكتشاف العديد من تفاعلات الارتباط المحتملة بين الجزيئات المقترحة و ''ب.ر.أ. ف-في. 600.إي''. أثبت ظهور الروابط الهيدروجينية والتفاعلات الكارهة للماء مع المخلفات الأساسية لـ ''ب.ر.أ. ف-في. 600.إي'' الثبات العالي لهذه المجمعات. أظهرت المركبات المختارة خصائص دوائية فائقة وفقا لقواعد التشابه الدوائي (التوافر البيولوجي) وخصائص الحرائك الدوائية. وبالمثل، تم حساب الطاقة الخاصة بالمدارات الجزيئية الحدودية مثل المدار الجزيئي الأعلى المشغول، وأدنى المدار الجزيئي غير المشغول، وفجوة الطاقة، ومعلمات التفاعل الأخرى باستخدام نظرية الكثافة الوظيفية. تم فحص الأسطح المدارية الجزيئية الحدودية والإمكانات الكهروستاتيكية لإثبات توزيعات كثافة الشحنة التي قد تكون مرتبطة بالنشاط المضاد للسرطان. الاستنتاجات: وبالتالي، تم التعرف على المركبات المختارة كضربات قوية لـ ''ب.ر.أ. ف-في. 600.إي''. بخصائص حركية دوائية فائقة، ويمكن اقتراحها كعقاقير مرشحة واعدة للسرطان. Abstract: Objectives: V600E-BRAF kinase is an essential therapeutic target in melanoma and other types of tumors. Because of its resistance to known inhibitors and the adverse effects of some identified inhibitors, investigation of new potent inhibitors is necessary. Methods: In the present work, in silico strategies such as molecular docking simulation, pharmacokinetic evaluation, and density functional theory (DFT) computations were used to identify potential V600E-BRAF inhibitors from a set of 72 anticancer compounds in the PubChem database. Results: Five top-ranked molecules (12, 15, 30, 31, and 35) with excellent docking scores (MolDock score ≥90 kcal mol−1, Rerank score ≥60 kcal mol−1) were selected. Several potential binding interactions were discovered between the molecules and V600E-BRAF. The formation of H-bonds and hydrophobic interactions with essential residues of V600E-BRAF suggested the high stability of these complexes. The selected compounds had excellent pharmacological properties according to the drug likeness rules (bioavailability) and pharmacokinetic properties. Similarly, the energy for the frontier molecular orbitals, such as the HOMO, LUMO, energy gap, and other reactivity parameters, was computed with DFT. The frontier molecular orbital surfaces and electrostatic potentials were investigated to demonstrate the charge-density distributions potentially associated with anticancer activity. Conclusion: The identified compounds were found to be potent hit compounds for V600E-BRAF inhibition with superior pharmacokinetic properties; therefore, they may be promising cancer drug candidates.

Traditional medicinal plant examination has increased in recent years since plants enable them to supplement current pharmaceutical treatments. In silico screening and pharmacokinetic screening, which employ computer mechanics, can increase the number of active compounds and reveal their mechanism of action. In silico ADME screening is less expensive, quicker, and more secure than in vivo ADME testing, which is lengthy, costly, and dangerous for animals. The SwissADME and protox‐II are free tools that offer free accessibility to various chemical attributes, after receiving the structures of the examined compounds in canonical SMILES format. A total of 50 viable compounds from mushrooms that had been previously described in the research were tested for ADME qualities and toxicity, and their outcomes were then analyzed. Future research will be aided by an understanding of a compound's ADME/T properties, and the findings will be helpful to scientists. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance is a growing concern, and the development of new anti-bacterial agents is crucial. 2-aminophenyl-2-(2,4,5-triphenylimidazole) derivatives have shown potential as anti-bacterial agents in previous studies, and this study aims to further explore their potential. Materials and Methods: Several 2-aminophenyl-2-(2,4,5-triphenylimidazole) derivatives have been developed and synthesized in this work. Using the disc diffusion technique, their anti-bacterial activity was assessed against Escherichia coli and Staphylococcus aureus. Additionally, the compounds' drug likeness and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics were assessed. To learn more about how chemical compounds attach to the biotin protein ligase, molecular docking investigations were carried out. Results: The synthesized compounds exhibited varying degrees of anti-bacterial activity, with AC6 showing the highest activity against both E. coli and S. aureus. The compounds were found to adhere to Lipinski's rule of five, indicating good drug likeness, and exhibited favourable ADMET properties. The molecular docking studies revealed that the compounds had favourable binding modes with biotin protein ligase (PDB ID: 4DQ2). Conclusion: The 2-aminophenyl-2- (2,4,5-triphenylimidazole) derivatives designed and synthesized in this study exhibited promising anti-bacterial activity against E. coli and S. aureus. The compounds also demonstrated good Drug likeness and favourable ADMET properties. The molecular docking studies provided insights into the binding modes of the compounds with biotin protein ligase. These results suggest that 2-aminophenyl-2-(2,4,5-triphenylimidazole) derivatives have potential as anti-bacterial agents and warrant further investigation. [ABSTRACT FROM AUTHOR]

Background. The contemporary antidiabetic drugs have side effects and adverse reactions. This demand to search for less toxic and effective treatments for diabetes from medicinal plants using computational methods. The present research investigated the molecular docking of Anacardium occidentale nut methanolic extract compounds with selected proteins related to diabetes and the compounds’ AMDET properties. Material and Methods. The compounds were identified using Gas chromatography-mass spectrometry analysis. The compounds'2-dimensional structure was retrieved from the PubChem compound database. Three-dimensional crystallographic structure of selected proteins; B-cell-lymphoma-2 (Bcl-2), caspase-3, glucocorticoids, interleukin-1β, myeloperoxidase and tumor necrosis factor-alpha (TNF-α) was downloaded from Protein Data Bank. Molecular docking was performed using Autodoc kvina and the active site of binding interactions was detected with the Computed Atlas of Surface Topography of proteins (CAST-P). The compounds' drug-likeness, physicochemical and ADMET were evaluated using molininspiration and admet-SAR online tools. Results. Ten compounds were identifi ed from the Anacardium occidentale nut methanolic extract. All the compounds exhibited drug-likeness properties with violation of one Lipinski’s rule. Two compounds, oleic acid and 3-(p-methoxyphenyl)-propionic acid exhibited the best binding energy with the active receptors site of Bcl-2, caspase-3, TNF-α and glucocorticoid. Also, tridecanoic acid exhibited good binding energy with the active site of glucocorticoid receptors. Only 3-(p-methoxyphenyl)-propionic acid exhibited moderate binding energy with the active receptors site of interleukin-1β and myeloperoxidase. All the compounds displayed excellent ADMET properties. Conclusions. Antidiabetic drugs with the least side effects could be explored from these compounds. [ABSTRACT FROM AUTHOR]

Computers have made it simpler to anticipate molecular characteristics, toxicity, and pharmacological efficacy in the quest for new drugs. Herbal drugs are seen as effective when they are targeted appropriately and have fewer negative effects. Due to the range of chemicals they contain, plants have been the basis for many pharmacological entities. Terpenoids and fatty acid esters compounds abound in the Tiliaceae herb Triumfetta pentandra. The plant has historically been used to treat a wide range of illnesses and conditions, including goiter, diabetes, hypertension, stomach disturbances, skin conditions, and fetal implanting. We describe Triumfetta pentandra terpenoids and fatty acid esters for the first time in terms of pharmacological similarity, toxicological characteristics, bioactivity score, and molecular targets. Molecular inspiration and the Osiris property explorer software were used to forecast the molecular properties, bioactivity, and toxicity of the phytochemicals. Swiss target prediction software was used to forecast the probability of the target protein. The compounds' bioactivities ranged from −3.75 to 0.21 for GPCR modulation, −3.63 to 1.08 for ion channel modulation, −3.84 to 0.57 for kinase, 0.02 to 0.52 for nuclear receptor ligand, −3.67 to 0.21 for protease, and 0.06 to 1.01 for enzyme. The compounds had multiple distinct protein targets with varying probabilities. Every compound followed the "rule of five," and they all had high drug efficacy ratings. Five compounds exhibited low to moderate toxicity; seven were non-toxic (green in hue); and four had inconsistent hazardous levels (red or orange in colour). This data can be used as a monograph by scientists researching novel medications. [ABSTRACT FROM AUTHOR]

A series of (E)-1-(3/4-{[(E)-(2-chloroquinolin-3-yl)methylidene]amino}phenyl)ethan-1-one oximes 3a–3j have been designed and synthesized by the condensation of 2-chloroquinoline-3-carbaldehydes and (E)-1-(3/4-aminophenyl)ethan-1-one oximes using glacial acetic acid as a catalyst. The structures of the newly synthesized compounds were characterized by 1H and 13C NMR, FT-IR, and mass spectra. All compounds 3a–3j were assessed for their drug likeness and ADMET properties using computational analysis. They showed optimal drug scores and negligible toxicities and satisfied Lipinskiʼs rule of five. Compounds 3f, 3h, and 3i exhibited significant antimicrobial activity against Gram-positive (S. aureus, B. subtilis) and Gram-negative bacteria (S. Typhi, P. aeruginosa) and fungi (A. niger, A. flavus), whereas compounds 3g–3j showed antimyco-bacterial activity against Mycobacterium tuberculosis H37Rv strain with MIC in the range of 1.6 to 100 µg/mL. [ABSTRACT FROM AUTHOR]

The prospective compound pencycuron (PNC) was probed using FT-IR, FT-Raman, NMR, and UV-Vis spectra and quantum chemical computation. Vibrational assignment pertaining to different modes of vibration with potential energy distribution has been augmented by normal coordinate analysis (NCA). The most stable minimum energy conformer was identified by performing potential energy surface scan (PES) along the rotational bonds at the B3LYP/6-311++G(d,p) level of theory. The chemical reactivity and stability of PNC were estimated based on the HOMO-LUMO energy gap and NBO approach. The overall picture of accumulation of charges on individual atoms of the molecule was predicted by molecular electrostatic potential (MEP) surface map which in turn identifies the nucleophilic and electrophilic region or sites. The intermolecular interaction in the PNC was confirmed by using Hirshfeld surfaces. Antifungal activity of the compound with different bacterial strains was validated by the agar well diffusion method. Ligand-protein interaction was explored by using molecular docking studies, while the pharmacokinetic aspects of the compound were probed using drug likeness and Absorption, Distribution, Metabolism, Excretion, and Toxicity properties. The stability of the title compound has been investigated via molecular dynamics simulation (MDS). [ABSTRACT FROM AUTHOR]

The optimized molecular geometry, vibrational assessments, natural bond orbital (NBO) analyses for 3-Methylpyridine were performed by B3LYP/6–311++G (d,p) functional. Computational vibrational frequencies and NMR spectra were compared with the recorded experimental data. The charge distribution, reactive areas, and electrostatic potential were well defined with the help of Molecular Electrostatic Potential surface (MEP) and Fukui functions. The energy difference between HOMO and LUMO revealed chemical activity of the titled molecule. Natural bond order analysis (NBO) was done to understand intermolecular charge transfer (ICT). Gibbs free energy, enthalpy and entropy were determined at different temperatures. Intermolecular interactions were studied via Hirshfeld surface showed 3-picoline stabilized mainly by formation of C–H/H–C contacts. The electron excitation analysis was carried out by drawing Hole, and Electron density distribution maps in excited states of higher oscillatory strength with DMSO, MeOH as solvents. Bioactivity of the molecule is calculated theoretically with the help of Electrophilicity index. Molecular docking was done to study interaction between ligand and protein. Drug likeness determined the nature of the molecule considering the use for medicinal purpose. A molecular dynamics simulation was used to explore biomolecular stability. [ABSTRACT FROM AUTHOR]

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The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a result, drug conjugates are an active area of research and development in medicinal chemistry. This research demonstrates acetamide–sulfonamide scaffold preparation after conjugation of ibuprofen and flurbiprofen with sulfa drugs, and these scaffolds were then screened for urease inhibition. The newly designed conjugates were confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and elemental analysis. Ibuprofen conjugated with sulfathiazole, flurbiprofen conjugated with sulfadiazine, and sulfamethoxazole were found to be potent and demonstrated a competitive mode of urease inhibition, with IC50 (µM) values of 9.95 ± 0.14, 16.74 ± 0.23, and 13.39 ± 0.11, respectively, and urease inhibition of 90.6, 84.1, and 86.1% respectively. Ibuprofen conjugated with sulfanilamide, sulfamerazine, and sulfacetamide, whereas flurbiprofen conjugated with sulfamerazine, and sulfacetamide exhibited a mixed mode of urease inhibition. Moreover, through molecular docking experiments, the urease receptor-binding mechanisms of competitive inhibitors were anticipated, and stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and that no conformational changes occurred during the simulation. The findings demonstrate that conjugates of approved therapeutic molecules may result in the development of novel classes of pharmacological agents for the treatment of various pathological conditions involving the urease enzyme. [ABSTRACT FROM AUTHOR]

A biologically promising new molecule, 3-(benzylthio)-4-hydroxy-2H-chromen-2-one has been synthesized following visible light-induced protocol in the presence of singlet molecular oxygen. Its detailed spectral properties and X-ray crystal structure are studied. The crystal structure is solved by direct method and refined to a final R value of 0.0701. The crystal structure is stabilized by an elaborate system of hydrogen bonds along with π–π and Van der Waal's forces to form supramolecular structures. 3D Hirshfeld surfaces and allied 2D fingerprint plots are analyzed for non-covalent interactions. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (38.2%) and C···H/H···C (22.4%) interactions. Energy framework analysis allowed us to quantify different contributions to the overall energy. Theoretical (DFT) studies on the molecular structure, Mulliken charges, HOMO, LUMO, MESP surfaces have been performed at B3LYP/6-311 + G(d,p) level of theory. The molecular docking studies are performed to get insights into the inhibition nature of this molecule against CDKS protein and for searching new anticancer agents. Pharmacological analysis was carried out in-order to check the bioactive nature of synthesized compound. [ABSTRACT FROM AUTHOR]

To discover anti-acetylcholinesterase agents for the treatment of Alzheimer's disease (AD), a series of novel Schiff base-coumarin hybrids was rationally designed, synthesized successfully, and structurally characterized using Fourier transform infrared (FTIR), Nuclear magnetic resonance (NMR), and High-Resolution Mass Spectrometry (HRMS) analyses. These hybrids were evaluated for their potential inhibitory effect on acetylcholinesterase (AChE). All of them exhibited excellent inhibitory activity against AChE. The IC50 values ranged from 87.84 to 515.59 μg/mL; hybrids 13c and 13d with IC50 values of 0.232 ± 0.011 and 0.190 ± 0.004 µM, respectively, showed the most potent activity as acetylcholinesterase inhibitors (AChEIs). The reference drug, Galantamine, yielded an IC50 of 1.142 ± 0.027 µM. Reactivity descriptors, including chemical potential (μ), chemical hardness (η), electrophilicity (ω), condensed Fukui function, and dual descriptors are calculated at wB97XD/6-311++ G (d,p) to identify reactivity changes of the designed compounds. An in-depth investigation of the natural charge pattern of the studied compounds led to a deep understanding of the important interaction centers between these compounds and the biological receptors of AChE. The molecular electrostatic surface potential (MESP) of the most active site in these derivatives was determined using high-quality information and visualization. Molecular docking analysis was performed to predict binding sites and binding energies. The structure-activity-property relationship studies indicated that the proposed compounds exhibit good oral bioavailability properties. To explore the stability and dynamic behavior of the ligand-receptor complexes, molecular dynamics simulations (MDS) were performed for 100 ns on the two best docked derivatives, 13c and 13d, with the AChE (4EY7) receptor. A popular method for determining the free binding energies (MM/GBSA) is performed using snapshots taken from the systems' trajectories at 100 ns. These results revealed that the complex system of compound 13d acquired a relatively more stable conformation and exhibited better descriptors than the complex system of compound 13c and the Galantamine drug, suggesting its potential as an effective inhibiting drug. The binding free energy analysis revealed that the 13d-4EY7 complex exhibited greater stability with AChE receptors compared to other complexes. [ABSTRACT FROM AUTHOR]

Isoxazole belongs to the class of five-membered heterocyclic compounds. The process of developing new drugs has significantly gained attention due to inadequate pharmacokinetic and safety attributes of the available drugs. This study aimed to design a new diverse array of ten novel isoxazole derivatives via Claisen Schmidt condensation reaction. In vitro COX-1/2 anti-inflammatory assay, in silico molecular docking of potent compounds, Molecular docking simulation, and SwissADME pharmacokinetic profile were investigated in this research. The in vitro COX-1 and COX-2 enzyme inhibitory assay showed that almost all the tested compounds exhibited anti-inflammatory effects whereas C6, C5, and C3 were found to be the most potent COX-2 enzyme inhibitors among the tested compounds and are good candidates for selective COX-2 inhibitors. In silico molecular docking studies coupled with molecular dynamic simulation has been done to rationalize the time-evolved mode of interaction of selected inhibitor inside the active pockets of target COX-2. The binding orientations and binding energy results also showed the selectivity of compounds towards COX-2. Physicochemical properties, pharmacokinetic profile, lipophilicity, water solubility, drug metabolism, drug-likeness properties, and medicinal chemistry of the synthesized isoxazole derivatives were assessed. The SwissADME (absorption, distribution, metabolism, and excretion) database was used to assess the physicochemical properties and drug-likeness properties of the synthesized isoxazole derivatives. All the compounds were shown high GI absorption except Compound 7 (C7). Compound 1 (C1) and Compound 2 (C2) were found to cross the blood-brain barrier (BBB). Lipinski’s rule of five is not violated by any of the ten synthesized isoxazole derivatives. It was predicted with the SwissADME database that C2, C5, C6, C7, and C8 are potent inhibitors of cytochrome (CYP) subtype CYP-2C19. A subtype of CYP-2C9 was inhibited by C4 and C7. The medicinal chemistry of all the compounds C1-C10 showed no PAIN (Pan assay interference compounds) alerts. The improved gastrointestinal (GI) absorption and BBB permeability of C1 and C2 can provide a future prospective for new researchers in the medicinal field to investigate the compounds for the management of chronic diseases. The synthesized isoxazole compounds showed excellent in vitro COX-1/2 enzymes anti-inflammatory investigations, in silico studies, good physicochemical properties, and improved pharmacokinetic profile which will be further investigated via in vivo anti-inflammatory activities. Moreover, to further support our findings of the computational research and in vitro studies, an in-vivo pharmacokinetic profile is suggested in the future.

Millets are becoming more popular as a healthy substitute for people with lifestyle disorders. They offer dietary fiber, polyphenols, fatty acids, minerals, vitamins, protein, and antioxidants. The nutritional importance of millets leads to the present in-silico study of selective bioactive compounds docked against the targets of lifestyle diseases, viz., diabetes, hypertension, and atherosclerosis using molecular docking and molecular simulations approach. Pharmacokinetic analysis was also carried out to analyse ADME properties and toxicity analysis, drug-likeliness, and finally target prediction for new targets for uncharacterized compounds or secondary targets for recognized molecules by Swiss Target Prediction was also done. The docking results revealed that the bioactive compound flavan-4-ol, among all the 50 compounds studied, best docked to all the four targets of lifestyle diseases, viz., Human dipeptidyl peptidase IV (−5.94 kcal mol−1 binding energy), Sodium-glucose cotransporter-2 (−6.49 kcal mol−1) diabetes-related enzyme, the Human angiotensin-converting enzyme (−6.31 kcal mol−1) which plays a significant role in hypertension, and Proprotein convertase subtilisin kexin type 9 (−4.67 kcal mol−1) for atherosclerosis. Molecular dynamics simulation analysis substantiates that the flavan-4-ol forms a better stability complex with all the targets. ADMET profiles further strengthened the candidature of the flavan-4-ol bioactive compound to be considered for trial as an inhibitor of targets DPPIV, SGLT2, PCSK9, and hACE. We suggest that more research be conducted, taking Flavon-4-ol into account where it can be used as standard treatment for lifestyle diseases.

Teshome Degfie,1 Japheth O Ombito,2 Taye B Demissie,2 Rajalakshmanan Eswaramoorthy,3 Aman Dekebo,1,4 Milkyas Endale1 1Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, Adama, Ethiopia; 2Department of Chemistry, University of Botswana, Gaborone, Botswana; 3Department of Biomaterials, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; 4Institute of Pharmaceutical Sciences, Adama Science and Technology University, Adama, EthiopiaCorrespondence: Milkyas Endale; Teshome Degfie, Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, P.O. Box 1888, Adama, Ethiopia, Email milkyas.endale@astu.edu.et; teshome2degfie@yahoo.comBackground: Cyphostemma cyphopetalum is a medicinal plant traditionally used to treat various ailments. Limited studies on C. cyphopetalum inspired us to investigate the chemical nature and therapeutic potential of the plant.Methods: Silica gel column chromatographic separation was used for isolation. 1D and 2D NMR spectroscopic analysis and literature data were used for structural elucidation. Agar well diffusion assay was used for evaluation of antibacterial activity against E. coli, P. aeruginosa, and S. aureus. DPPH assay was used to evaluate radical scavenging activities. Molecular docking was done by AutoDock Vina 4.2 open-source program. DFT calculations were performed using the Gaussian 16 program package.Results: Dichloromethane/methanol (1:1) roots extract afforded a new hydroxyl-spongiane diterpenoid lactone derivative, 3-hydroxyisoagatholactone ( 1), along with β-sitosterol ( 2) and ϵ-viniferin ( 3) whereas methanol extract afforded trans-resveratrol ( 4), gnetin H ( 5), tricuspidatol A ( 6), ϵ-viniferin-diol ( 7) and parthenostilbenin B ( 8). At 50 μg/mL whereas compound 3 recorded the highest inhibition against E. coli (8.55 ± 0.45 mm) and S. aureus (9.30 ± 1.39 mm). Against P. aeruginosa, compound 5 consistently outperformed chloramphenicol (11.76 ± 0.77 mm, at 30 g/mL). Maximum binding affinity were observed by compound 3 against DNA gyrase B (-7.6 kcal/mol) where as compound 5 displayed maximum binding against PqsA (-8.8 kcal/mol) and S. aureus PK (-5.8 kcal/mol). Compounds 1, 3 and 4 satisfy Lipinski’s rule of five. Trans-resveratrol ( 4) demonstrated strong DPPH scavenging activity at 12.5 g/mL, with IC50 values of 0.052 μg/mL, compared to ascorbic acid (IC50 value of 0.0012 μg/mL).Conclusion: In this work, eight compounds were identified from the roots extracts of C. cyphopetalum including a new hydroxyl-spongiane diterpenoid lactone, 3-hydroxyisoagatholactone ( 1). Compounds 3 and 5 exhibited good antibacterial activity and binding affinities. The docking result is in agreement with the in vitro antibacterial study. Overall, the study result suggests that the isolated compounds have the potential to be used as therapeutic agents, which supports the traditional uses of C. cyphpetalum roots.Keywords: Cyphostemma cyphopetalum, 3-hydroxyisoagatolactone, antibacterial, docking, drug-likeness, antioxidant studies

The DFT B3LYP-LAND2DZ technique is used to examine interactions of Methyl nicotinate with copper selenide and zinc selenide clusters. The existence of reactive sites is determined using ESP maps and Fukui data. The energy variations between HOMO and LUMO are utilised to calculate various energy parameters. The Atoms in Molecules and ELF (Electron Localisation Function) maps are employed to investigate the topology of the molecule. The Interaction Region Indicator is used to determine the existence of non-covalent zones in the molecule. The UV–Vis spectrum using the TD-DFT method and DOS graphs are used to obtain the theoretical determination of electronic transition and properties. Structural analysis of the compound is obtained using theoretical IR spectra. To explore the adsorption of copper selenide and zinc selenide clusters on the Methyl nicotinate, the adsorption energy and theoretical SERS spectra are employed. Furthermore, pharmacological investigations are carried out to confirm the drug's non-toxicity. The compound's antiviral efficacy against HIV and Omicron is demonstrated via protein-ligand docking.

Virtual screening of the potential lead chemotherapeutic phytochemicals from medicinal plants has useful application in the field of in-silico modelling and computer-based drug design by orienting and scoring ligands in the active binding site of a target protein. The phytochemical investigation of the Pterocephalus frutescens extract in n-butanol resulted in the isolation and structure elucidation of three iridoids and four flavonoids which were identified as Geniposide (1), Geniposidic acid (2), Nepetanudoside C (3), Isovitexin (4), Luteolin-7-O-glucoside (5) Isoorientin (6) and Orientin (7), respectively. Molecular docking studies were used to compare the binding energies of the isolated phytochemicals at four biological cancer-relevant targets; namely, aromatase, carbonic anhydrase IX, fatty acid synthase, and topoisomerase II-DNA complex. The docking study concluded that the isolated compounds have promising cytotoxic activities, in particular, Luteolin-7-O-glucoside (5) and Orientin (7) which exhibited high binding affinities among the isolated compounds at the active sites of the target enzymes; Aromatase (−8.73 Kcal/mol), and Carbonic anhydrase IX (−8.92 Kcal/mol), respectively, surpassing the corresponding binding scores of the co-crystallized ligands and the reference drugs at these target enzymes. Additionally, among the isolated compounds, Luteolin-7-O-glucoside (5) showed the most outstanding binding affinities at the active sites of the target enzymes; Fatty acid synthase, and Topisomerase II-DNA complex with binding scores of −6.82, and −7.99 Kcal/mol, respectively. Finally, the SwissADME online web tool predicted that most of these compounds possessed acceptable oral bioavailability and drug likeness characteristics. [ABSTRACT FROM AUTHOR]

A series of novel pyrazole-integrated 1,3,4-oxadiazole derivatives have been synthesized and characterized by 1H and 13C NMR, IR, and mass spectra and elemental analyses. The synthesized compounds were docked at the active site of cyclin-dependent kinase 2 (CDK2) protein using the Glide tool of the Schrödinger Suite. The compounds were optimized based on glide score, glide energy, binding free energy (from Prime MM/GBSA), and bioavailability and compared to the reference drugs Milciclib and Trilaciclib reported as CDK2 inhibitors. The molecular docking study revealed that the synthesized compounds showed better drug likeness than the existing drugs by binding to the active site of CDK2 protein. [ABSTRACT FROM AUTHOR]

Breynia cernua has been used as an alternative medicine for wounds, smallpox, cervical cancer, and breast cancer. This plant is a potential source of new plant-derived drugs to cure numerous diseases for its multiple therapeutic functions. An in vitro study revealed that the methanol extract of B. cernua (stem) exhibits antioxidant activity according to DPPH and SOD methods, with IC50 values of 33 and 8.13 ppm, respectively. The extract also exerts antibacterial activity against Staphylococcus aureus with minimum bactericidal concentration of 1875 ppm. Further analysis revealed that the extract with a concentration of 1–2 ppm protects erythrocytes from the ring formation stage of Plasmodium falciparum, while the extract with a concentration of 1600 ppm induced apoptosis in the MCF-7 breast cancer cell line. GC–MS analysis showed 45 bioactive compounds consisting of cyclic, alkyl halide, organosulfur, and organoarsenic compounds. Virtual screening via a blind docking approach was conducted to analyze the binding affinity of each metabolite against various target proteins. The results unveiled that two compounds, namely, N-[β-hydroxy-β-[4-[1-adamantyl-6,8-dichloro]quinolyl]ethyl]piperidine and 1,3-phenylene, bis(3-phenylpropenoate), demonstrated the best binding score toward four tested proteins with a binding affinity varying from −8.3 to −10.8 kcal/mol. Site-specific docking analysis showed that the two compounds showed similar binding energy with native ligands. This finding indicated that the two phenolic compounds could be novel antioxidant, antibacterial, antiplasmodial, and anticancer drugs. A thorough analysis by monitoring drug likeness and pharmacokinetics revealed that almost all the identified compounds can be considered as drugs, and they have good solubility, oral bioavailability, and synthetic accessibility. Altogether, the in vitro and in silico analysis suggested that the extract of B. cernua (stem) contains various compounds that might be correlated with its bioactivities. [ABSTRACT FROM AUTHOR]

[Display omitted] • The molecular structure of 2BCA and its conformer was examined. • The molecular analysed using FT-IR, FT-Raman, NMR, and UV–Vis techniques. • The charge transfer in the molecule is investigated by examining the FMO in relation to NBO research. • The compound's chemical shift is determined, indicating a favourable change in it. • The assignments are completed based on the Total Energy Distribution (TED). The molecule of 2-Biphenyl Carboxylic Acid (2BCA), which contains peculiar features, was explored making use of density functional theory (DFT) and experimental approaches in the area of quantum computational research. The optimised structure, atomic charges, vibrational frequencies, electrical properties, electrostatic potential surface (ESP), natural bond orbital analysis and potential energy surface (PES) were obtained applying the B3LYP approach with the 6–311++ G (d,p) basis set.. The 2BCA molecule was examined for possible conformers using a PES scan. The methods applied for spectral analyses included FT-IR, FT-RAMAN, NMR, and UV–Vis results. Vibrational frequencies for all typical modes of vibration were found using the Potential Energy Distribution (PED) data. The UV–Vis spectrum was simulated using the TD-DFT technique, which is also seen empirically. The Gauge-Invariant Atomic Orbital (GIAO) approach was employed to model and study the 13C and 1H NMR spectra of the 2BCA molecule in a CDCL3 solution. The spectra were then exploited experimentally to establish their chemical shifts. To predict the donor and acceptor interaction, the NBO analysis was used. The electrostatic potential surface was employed to anticipate the locations of nucleophilic and electrophilic sites. Hirshfeld surfaces and their related fingerprint plots are exploited for the investigation of intermolecular interactions. Reduced Density Gradient (RDG) helps to measure and illustrate electron correlation effects, offering precise insights into chemical bonding, reactivity, and the electronic structure of 2BCA. According to Lipinski and Veber's drug similarity criteria, 2BCA exhibits the typical physicochemical and pharmacokinetic properties that make it a potential oral pharmaceutical candidate. According to the findings of a molecular docking study, the 2BCA molecule has promise as a treatment agent for the Nipah virus (PDB ID: 6 EB9), which causes severe respiratory and neurological symptoms in humans. [ABSTRACT FROM AUTHOR]

Computational pharmacology and chemistry of drug-like properties along with pharmacokinetic studies have made it more amenable to decide or predict a potential drug candidate. 4-Hydroxyisoleucine is a pharmacologically active natural product with prominent antidiabetic properties. In this study, ADMETLab 2.0 was used to determine its important drug-related properties. 4-Hydroxyisoleucine is compliant with important drug-like physicochemical properties and pharma giants’ drug-ability rules like Lipinski’s, Pfizer, and GlaxoSmithKline (GSK) rules. Pharmacokinetically, it has been predicted to have satisfactory cell permeability. Blood–brain barrier permeation may add central nervous system (CNS) effects, while a very slight probability of being CYP2C9 substrate exists. None of the well-known toxicities were predicted in silico, being congruent with wet lab results, except for a “very slight risk” for respiratory toxicity predicted. The molecule is non ecotoxic as analyzed with common indicators such as bioconcentration and LC50 for fathead minnow and daphnia magna. The toxicity parameters identified 4-hydroxyisoleucine as non-toxic to androgen receptors, PPAR-γ, mitochondrial membrane receptor, heat shock element, and p53. However, out of seven parameters, not even a single toxicophore was found. The density functional theory (DFT) study provided support to the findings obtained from drug-like property predictions. Hence, it is a very logical approach to proceed further with a detailed pharmacokinetics and drug development process for 4-hydroxyisoleucine.

The present research is focused on new findings of azaphenothiazine analogs which is the promising lead moiety as the phenothiazine ring modified with azine ring as the basic nucleus reported from the literature survey that it has a wide spread of biological activity. The fifteen compounds were subjected to a molecular docking investigation using autodock pyrex, and it was discovered that ligand 4 with an ethyl group replaced gave the receptor a strong binding affinity of -8.6. Ligand 6having methyl group (showed the lowest binding affinity of -7.8. ligand 10 which is a substituted chlorine group gave good binding affinity and Ligand 13 showed significant binding affinity of -7.4 and -7.3 for the 2CMF active site of Acetylcholine esterase enzyme compared to imipramine (standard). The ADME property of selected moiety which is most important for drug development and discovery was done using SWISS adme and obeyed Lipinski rule 5 which plays an important role to predict physiochemical properties. [ABSTRACT FROM AUTHOR]

Aim To isolate and characterize anti- Candida compounds from soil actinobacterium Streptomyces chrestomyceticus ADP4 and to assess their drug likeness. Methods and Results Two anti- Candida compounds, Phenyl 2′α, 2′β, 6′β-trimethyl cyclohexyl ketone (1PB1) and Phenyl nonanyl ether (1PB2), were isolated from the metabolites produced by Streptomyces chrestomyceticus ADP4. Their structures were deduced by extensive analyses of spectral data obtained from liquid chromatography with tandem mass spectrometry (LCMS/MS), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR) and ultraviolet (UV) spectroscopies. While both the compounds inhibited growth of the Candida spp. 1PB2 was effective in inhibiting biofilm formed by Candida albicans ATCC 10231. The compounds did not show any cytotoxicity against HepG2 cells and were found to be safe when predicted theoretically on rat model, bioaccumulation and mutagenicity by using the software: toxicity estimation software tool (TEST). The compounds displayed drug-like properties when analyzed by using SwissADME software. Conclusions 1PB1 and 1PB2 are being reported for the first time from any natural source along with their anti- Candida properties. In-silico studies revealed their druggability and suitability to take up further work on the compounds for their possible application in treating Candida -associated infections. Significance and impact of the study The increasing prevalence of Candidiasis associated with drug-resistant strains of Candida spp. highlighted the urgent need for discovery of new compounds with anti- Candida properties that could hold promise as potential drug candidate. [ABSTRACT FROM AUTHOR]

• Out of 45917 natural compounds, about thirty phyto components had a higher binding affinity and inhibited Papain-Like Proteases (PLpro). • All the selected compounds obey the ADMET properties. • When compared to remidisevir, ritonavir, and lopinavir, SN00334175 and SN00162745 had better docking scores. • SN00334175/7JN2 and SN00162745/7JN2 demonstrated that these complexes were stabilised by ligand binding interactions with Gly266, Asn267, Tyr268, Tyr273, Thr301, and Asp302, Lys157, Leu162, Asp164, Arg166, Glu167, Pro248, Tyr264, respectively. • Plant Based medicine may possess potent inhibitors against SARS-CoV-2 Coronaviruses (CoVs) are a large group of enveloped positive sense single-stranded RNA viruses that can cause disease to humans. These are zoonotic having potential to cause large-scale outbreaks of infections widely causing morbidity and mortality. Papain-Like Protease (PLpro) is a cysteine protease, essential for viral replication and proliferation, as a highly conserved enzyme it cleaves peptide linkage between Nsp1, Nsp2, Nsp3, and Nsp4. As a valid therapeutic target, it stops viral reproduction and boosts host immune response thereby halting further spread of infection. In the purpose of identifying inhibitors targeting Papain-Like Proteases (PLpro) we initiated a high throughput virtual screening (HTVS) protocol using a SuperNatural Database. The XP docking results revealed that two compounds SN00334175 and SN00162745 exhibited docking scores of -10.58 kcal/mol and -9.93 kcal/mol respectively. The Further PRIME MMGB-SA studies revealed Van der Waal energy and hydrophobic energy terms as major contributors for total binding free energy. The 100 ns molecular dynamics simulation of SN00334175/7JN2 and SN00162745/7JN2 revealed that these complexes were stabilized with ligand binding forming interactions with Gly266, Asn267, Tyr268, Tyr273, Thr301 and Asp302, Lys157, Leu162, Asp164, Arg166, Glu167, Pro248 and Tyr264. [ABSTRACT FROM AUTHOR]

A series of 1,4-disubstituted anthraquinone analogs with amide, benzene sulfonamide, and hydrophobic functional features have been designed and synthesized. The structure of newly developed anthraquinone compounds (B141–B148) has been confirmed on FT-IR, 1H-NMR, 13C-NMR, and HR-MS spectroscopic tools. These synthesized anthraquinone compounds (B141–B148) and standard drug Mitoxantrone have been screened for biological activities using molinspiration and osiris property explorer, indicating that the compounds have smaller groups (–CH2– and –CH2–CH2–) in the side chain are orally active in comparison to other synthesized compounds. Cytotoxic study has been carried out on MCF-7, PC-3, and Hela cell lines using SRB assay. Synthesized anthraquinone compounds were found to be ineffective in the tested concentration range (10–80 μg/mL) on Hela and PC-3 cell lines. But, B147 and B148 compounds with a smaller alkyl group (–CH2–) on the side chain are screened out to be the best among all synthesized compounds in the case of MCF-7 cell line. The reactivity of developed anthraquinone compounds was further explored by computational study. HOMO-LUMO energy gap and softness of molecule with the basis set as DFT/B3LYP/6-31G(d,p) have been studied. All the synthesized compounds (B141–B148) show energy gap comparable to that of the standard drug Mitoxantrone due to some structural similarity. The binding mode and extent of binding with ct-DNA have been studied for all synthesized anthraquinone compounds (B141–B148) and Mitoxantrone at different D/P ratios using absorption, emission, and viscometric techniques. Partial intercalation mode followed by external mode of binding of drugs with ct-DNA has been observed. FT-IR spectral titrations have also been carried out for Mitoxantrone. Compounds B147 and B148 are come out as the best. The FT-IR study supports the finding of absorption, emission, and viscometric analysis, with no conformational changes observed for ct-DNA backbone. The polar functional feature attached in the side chain stabilizes the anthraquinone derivatives via external binding. Structural characterization of series of synthesized anthraquinone derivatives (B141–B148) having amide, benzene/toluene sulfonamide, and hydrophobic features at 1 and 4 positions. Biological screening of synthesized anthraquinone derivatives (B141–B148) and Mitoxantrone (MTX) using molinspiration and Osiris property explorer along with anticancer screening against MCF-7, PC-3, and Hela cell lines. Interaction study of synthesized anthraquinone derivatives (B141–B148) and Mitoxantrone with ct-DNA using absorption, emission, and viscometric techniques. FT-IR spectral study on best-screened compounds B147, B148 and Mitoxantrone with ct-DNA. Docking of synthesized anthraquinone compounds (B141–B148) and Mitoxantrone with B-DNA. Computational study to relate the structure and reactivity of synthesized anthraquinone compounds (B141–B148) and Mitoxantrone using DFT/B3LYP/6-31G(d,p) method. [ABSTRACT FROM AUTHOR]

In the year 2019–2020, the whole world witnessed the spread of a disease called COVID-19 caused by SARS-CoV-2. A number of effective drugs and vaccine has been formulated to combat this outbreak. For the development of anti-COVID-19 drugs, the main protease (Mpro) is considered a key target as it has rare mutations and plays a crucial role in the replication of the SARS CoV-2. In this study, a library of selected lichen compounds was prepared and used for virtual screening against SARS-CoV-2 Mpro using molecular docking, and several hits as potential inhibitors were identified. Remdesivir was used as a standard inhibitor of Mpro for its comparison with the identified hits. Twenty-six compounds were identified as potential hits against Mpro, and these were subjected to in silico ADMET property prediction, and the compounds having favorable properties were selected for further analysis. After manual inspection of their interaction with the binding pocket of Mpro and binding affinity score, four compounds, namely, variolaric acid, cryptostictinolide, gyrophoric acid, and usnic acid, were selected for molecular dynamics study to evaluate the stability of complex. The molecular dynamics results indicated that except cryptostictinolide, all the three compounds made a stable complex with Mpro throughout a 100-ns simulation time period. Among all, usnic acid seems to be more stable and effective against SARS-CoV-2 Mpro. In summary, our findings suggest that usnic acid, variolaric acid, and gyrophoric acid have potential to inhibit SARS-Cov-2 Mpro and act as a lead compounds for the development of antiviral drug candidates against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the stem bark of Anthocephalus cadamba(Rubiaceae) led to the isolation of total ten secondary metabolites (1‐10) including β–sitosterol (1), ursolic acid (2), vanillic acid (3), quinovic acid (4), 3‐O‐[α‐L‐rhamnopyranosyl]‐quinovic acid (5), β‐sitosterol β‐D‐glucoside (6), cadambine (7), 3β‐dihydrocadambine (8), 7‐O‐acetyl loganin (9) and hexyl p‐coumarate (10). Four acetylated derivatives 2 a,5 a,7 aand8 aobtained through acetylation of compounds 2, 5, 7 and 8 respectively. All the compounds characterized using 1H and 13CNMR, HRESIMS and IR and comparison with literature. Compound 4showed the best cytotoxic activity with IC50 value 4 and 7 μM against pancreatic (MIA‐pa‐Ca‐2) and leukemia (HL‐60) cancer cells respectively. Docking results supported the anticancer potential of compound 4via inhibition of EGFR receptor (PDB ID:3POZ) and its pharmacokinetic profile found optimized as per the Lipinski's filter. Therefore compound 4has the potential to be developed as an anticancer agent against pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of Psoralea corylifolia seeds as a potential source of anticancer lead molecules led to the isolation of total fourteen secondary metabolites (1–14) bakuchiol (1), isopsoralen (2), psoralen (3), bavachinin (4), 4‐O‐methylbavachalcone (5), bavachalcone (6), 12, 13‐Dihydro‐12, 13‐epoxybakuchiol (7), corylin (8), psoralidin (9) neocorylin (10), corylifol A (11), neobavaisoflavone (12), bavachin (13) and 12‐hydroxyisobakuchiol (14). Their structures were confirmed by 1DNMR, MASS spectra and comparison with the literature. Compounds 10, 11, 13 and 14 exhibited promising in vitro anticancer activity further supported by in‐silico docking results against BRCA‐1 (PDB ID: 4OFB). Bavachin 13 was found as the most promising cytotoxic metabolite with IC50 value 2.22 μM against MCF‐7 cells. In‐vitro mechanism of action studies of 13 against MCF‐7 cell line showed apoptotic cleavage. In addition, most of the compounds showed good ADMET and drug likeness profile. Cumulative in‐vitro and in‐silico results provided compound 13 as a potential anticancer agent against breast cancer cells. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the leading cancer diseases, with 8% of death caused due to CRC worldwide. There are many pathways associated with the development of CRC and in that the Wnt/ß-catenin pathway protein, which plays a major role in cell proliferation, is selected for the docking studies. Wnt protein binds to the receptor and causes accumulation of ß-catenin in the cytosol. Thienopyrimidines are the fused pyrimidines along with five-membered hetero aromatic ring, which are the structural analog of biogenic purine. Thienopyrimidines are substituted with N-methyl piperazine and various anilines. This research is focused on to inhibit the Wnt protein from bind to the receptor using thienopyrimidine molecules as ligand by an in-silico approach (molecular docking, pharmacokinetics). The Wnt protein (PDB ID-4A0P) as a receptor and substituted thienopyrimidine molecules as a ligand are docked using PyRx software. The drug likeliness property is predicted by SwissADME. Based on the scoring function obtained by docking, the ligand TP02 is showing the highest binding energy of -9.0 Kcal/mol compared to the standard Bevacizumab Avastin -7.9Kcal/mol. Compounds TP04, TP07, TP08, TP17, and TP19 are also the best candidates and are not violating the criteria of Lipinski's rule and ADME (Absorption, Distribution, Metabolism, Excretion) properties. These results indicated that thienopyrimidine derivatives could be one of the leads for the treatment of colon cancer. [ABSTRACT FROM AUTHOR]

A new Schiff base was prepared by the condensation between the sulfa drug sulfadiazine and 5-nitrovanilline to form 4-((4-hydroxy-3-methoxy-5-nitrobenzylidene) amino)-N-(pyrimidin-2-yl) benzene sulfonamide (5NVDA). Spectral studies have been performed to confirm the structure of the compound. Electronic structure of the compound was studied using DFT B3LYP/aug-cc-pVDZ level. Detailed potential energy distribution and vibrational assignments were made with the help of scaled simulated spectrum. UV spectra in DMSO medium showed a strong peak at 335 nm, which is in consistent with TDDFT simulations using CAM-B3LYP functional. Frontier orbitals were analyzed and found that the compound is easily polarizable, but stable. The compound was stabilized by extensive delolcaltaion of electrons. Durg likeness studies proved that this compound is an ideal candidate to be used as a drug and PASS studies showed that it shows binding to HIV RNA activity, which is confirmed by molecular docking studies with docking score of −8.4 kcal/mol. [ABSTRACT FROM AUTHOR]

Abstract Background Thiazole-based Schiff base compounds display significant pharmacological potential with an ability to modulate the activity of many enzymes involved in metabolism. They also demonstrated to have antibacterial, antifungal, anti-inflammatory, antioxidant, and antiproliferative activities. In this work, conventional and green approaches using ZnO nanoparticles as catalyst were used to synthesize thiazole-based Schiff base compounds. Results Among the synthesized compounds, 11 showed good activities towards Gram-negative E. coli (14.40 ± 0.04), and Gram-positive S. aureus (15.00 ± 0.01 mm), respectively, at 200 μg/mL compared to amoxicillin (18.00 ± 0.01 mm and 17.00 ± 0.04). Compounds 7 and 9 displayed better DPPH radical scavenging potency with IC50 values of 3.6 and 3.65 μg/mL, respectively, compared to ascorbic acid (3.91 μg/mL). The binding affinity of the synthesized compounds against DNA gyrase B is within − 7.5 to − 6.0 kcal/mol, compared to amoxicillin (− 6.1 kcal/mol). The highest binding affinity was achieved for compounds 9 and 11 (− 6.9, and − 7.5 kcal/mol, respectively). Compounds 7 and 9 displayed the binding affinity values of − 5.3 to − 5.2 kcal/mol, respectively, against human peroxiredoxin 5. These values are higher than that of ascorbic acid (− 4.9 kcal/mol), in good agreement with the experimental findings. In silico cytotoxicity predictions showed that the synthesized compounds Lethal Dose (LD50) value are class three (50 ≤ LD50 ≤ 300), indicating that the compounds could be categorized under toxic class. Density functional theory calculations showed that the synthesized compounds have small band gap energies ranging from 1.795 to 2.242 eV, demonstrating that the compounds have good reactivities. Conclusions The synthesized compounds showed moderate to high antibacterial and antioxidant activities. The in vitro antibacterial activity and molecular docking analysis showed that compound 11 is a promising antibacterial therapeutics agent against E. coli, whereas compounds 7 and 9 were found to be promising antioxidant agents. Moreover, the green synthesis approach using ZnO nanoparticles as catalyst was found to be a very efficient method to synthesize biologically active compounds compared to the conventional method.

s of new 4-quinolone derivatives was synthesized by conventional heating method. For the synthesized compounds, we performed pharmacokinetic prediction, SAR and antimicrobial assay. The presence of halogen elements plays a key role in the biological activity that is clear by in vitro analysis. Target compounds exhibit moderate to significant activity near to standard marketed drugs like amoxycillin, chloramphenicol, ciprofloxacin, norfloxacin, griseofulvin, and nystatin. [ABSTRACT FROM AUTHOR]

A new library of structurally modified 3-(piperazin-1-yl)-1,2-benzothiazole derivatives have been designed and synthesized through a multi-step procedure. Their structures were characterized by IR, 1H NMR, 13C NMR, and mass spectral technique. The synthesized compounds were evaluated for drug likeness or "drugability" according to Lipinski's rule of five (RO5). One of the compounds showed two violations, whereas the others complied with RO5. The synthesized compounds were also screened for their antibacterial activity by the agar diffusion method, and three of them were found to be active. One of the compounds showed a good activity against Bacillus subtilis and Staphylococcus aureus with MIC 500 µg/mL. The compound with RO5 violations exhibited almost no antibacterial activity. [ABSTRACT FROM AUTHOR]

A panel of 2,3-disubstituted thiazolidin-4-ones 4a-n was synthesised from Schiff bases 3a-n derived from sulfanilamide, by reaction with thioglycolic acid. The compounds were characterised by means of IR, NMR, and Mass spectral data. Compounds 4a-n were screened for DPPH scavenging assay and compounds 4e, 4h, 4i, and 4n exhibited moderate activity. Compounds 4e, 4h, and 4i were tested at 200 mg/kg and 4e at 50 mg/kg b.w. orally for antidiabetic activity in fructose induced diabetic rats. They exhibited significant antidiabetic activity compared to the control group. Pioglitazone was used as a standard drug. The tested compounds exhibited better and ignificant serum cholesterol lowering activity when compared with the control and standard groups. They also reduced the triglyceride level after the 21st day; however, it was insignificant when compared to the control group. Compound 4n displayed the highest binding energy when docked with PPAR-γ followed by compounds 4e, 4h, and 4i when compared to pioglitazone. The physicochemical, drug likeness and ADME properties of the title compounds were found to be satisfactory. [ABSTRACT FROM AUTHOR]

Moringa oleifera Lam. (Moringaceae) is an adaptable plant with promising phytoconstituents, interesting medicinal uses, and nutritional importance. Chemical profiling of M. oleifera seeds assisted by LC-HRMS (HPLC system coupled to a high resolution mass detector) led to the dereplication of 19 metabolites. Additionally, the wound healing potential of M. oleifera seed extract was investigated in male New Zealand Dutch strain albino rabbits and supported by histopathological examinations. Moreover, the molecular mechanisms were investigated via different in vitro investigations and through analyzing the relative gene and protein expression patterns. When compared to the untreated and MEBO®-treated groups, topical administration of M. oleifera extract on excision wounds resulted in a substantial increase in wound healing rate (p < 0.001), elevating TGF-β1, VEGF, Type I collagen relative expression, and reducing inflammatory markers such as IL-1β and TNF-α. In vitro antioxidant assays showed that the extract displayed strong scavenging effects to peroxides and superoxide free radicals. In silico studies using a molecular docking approach against TNF-α, TGFBR1, and IL-1β showed that some metabolites in M. oleifera seed extract can bind to the active sites of three wound-healing related proteins. Protein–protein interaction (PPI) and compound–protein interaction (CPI) networks were constructed as well. Quercetin, caffeic acid, and kaempferol showed the highest connectivity with the putative proteins. In silico drug likeness studies revealed that almost all compounds comply with both Lipinski's and Veber's rule. According to the previous findings, an in vitro study was carried out on the pure compounds, including quercetin, kaempferol, and caffeic acid (identified from M. oleifera) to validate the proposed approach and to verify their potential effectiveness. Their inhibitory potential was evaluated against the pro-inflammatory cytokine IL-6 and against the endopeptidase MMPs (matrix metalloproteinases) subtype I and II, with highest activity being observed for kaempferol. Hence, M. oleifera seeds could be a promising source of bioactive compounds with potential antioxidant and wound healing capabilities. [ABSTRACT FROM AUTHOR]