Anticancer,Anticoagulant, Antioxidant and Antimicrobial Activities of Thevetia peruviana Latex with Molecular Docking of Antimicrobial and Anticancer Activities

Natural origin molecules represent reliable and excellent sources to overcome some medicinal problems. The study of anticancer, anticoagulant, and antimicrobial activities of Thevetia peruviana latex were the aim of the current research. An investigation using high-performance liquid chromatography (HPLC) revealed that the major content of the flavonoids are rutin (11.45 µg/mL), quersestin (7.15 µg/mL), naringin (5.25 µg/mL), and hisperdin (6.07 µg/mL), while phenolic had chlorogenic (12.39 µg/mL), syringenic (7.45 µg/mL), and ferulic (5.07 µg/mL) acids in latex of T. peruviana. Via 1,1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging, the experiment demonstrated that latex had a potent antioxidant activity with the IC₅₀ 43.9 µg/mL for scavenging DPPH. Hemolysis inhibition was 58.5% at 1000 µg/mL of latex compared with 91.0% at 200 µg/mL of indomethacin as positive control. Negligible anticoagulant properties of latex were reported where the recorded time was 11.9 s of prothrombin time (PT) and 29.2 s of the activated partial thromboplastin time (APTT) at 25 µg/mL, compared with the same concentration of heparin (PT 94.6 s and APPT 117.7 s). The anticancer potential of latex was recorded against PC-3 (97.11% toxicity) and MCF-7 (96.23% toxicity) at 1000 μg/mL with IC₅₀ 48.26 μg/mL and 40.31 µg/mL, respectively. Disc diffusion assessment for antimicrobial activity recorded that the most sensitive tested microorganisms to latex were Bacillus subtilis followed by Escherichia coli, with an inhibition zone (IZ) of 31 mm with minimum inhibitory concentration (MIC) (10.2 μg/mL) and 30 mm (MIC, 12.51 μg/mL), respectively. Moreover, Candida albicans was sensitive (IZ, 28 mm) to latex, unlike black fungus (Mucor circinelloides). TEM examination exhibited ultrastructure changes in cell walls and cell membranes of Staphylococcus aureus and Pseudomonas aeruginosa treated with latex. Energy scores of the molecular docking of chlorogenic acid with E. coli DNA (7C7N), and Rutin with human prostate-specific antigen (3QUM) and breast cancer-associated protein (1JNX), result in excellent harmony with the experimental results. The outcome of research recommended that the latex is rich in constituents and considered a promising source that contributes to fighting cancer and pathogenic microorganisms.     

Lipase-Catalyzed Synthesis,Antioxidant Activity,Antimicrobial Properties and Molecular Docking Studies of Butyl Dihydrocaffeate

Green chemistry approaches, such as lipase-catalyzed esterification, are promising methods for obtaining valuable chemical compounds. In the case of the use of lipases, unlike in aqueous environments, the processes of the ester bond formations are encountered in organic solvents. The aim of the current research was to carry out the lipase-catalyzed synthesis of an ester of dihydrocaffeic acid. The synthesized compound was then evaluated for antioxidant and antimicrobial activities. However, the vast majority of its antioxidant activity was retained, which was demonstrated by means of DPPH· (2,2-diphenyl-1-picrylhydrazyl) and CUPRAC (cupric ion reducing antioxidant capacity) methods. Regarding its antimicrobial properties, the antifungal activity against Rhizopus oryzae is worth mentioning. The minimum inhibitory and fungicidal concentrations were 1 and 2 mM, respectively. The high antifungal activity prompted the use of molecular docking studies to verify potential protein targets for butyl ester of dihydrocaffeic ester. In the case of one fungal protein, namely 14-α sterol demethylase B, it was observed that the ester had comparable binding energy to the triazole medication, isavuconazole, but the interacted amino acid residues were different.     

Chemical Composition,Antioxidant and Enzyme Inhibitory Activities of Onosma bourgaei and Onosma trachytricha and in Silico Molecular Docking Analysis of Dominant Compounds

The aim of this study was to investigate the chemical composition, antioxidant and enzyme inhibitory activities of methanol (MeOH) extracts from Onosma bourgaei (Boiss.) and O. trachytricha (Boiss.). In addition, the interactions between phytochemicals found in extracts in high amounts and the target enzymes in question were revealed at the molecular scale by performing in silico molecular docking simulations. While the total amount of flavonoid compounds was higher in O. bourgaei, O. trachytricha was richer in phenolics. Chromatographic analysis showed that the major compounds of the extracts were luteolin 7-glucoside, apigenin 7-glucoside and rosmarinic acid. With the exception of the ferrous ion chelating assay, O. trachytricha exhibited higher antioxidant activity than O. bourgaei. O. bourgaei exhibited also slightly higher activity on digestive enzymes. The inhibitory activities of the Onosma species on tyrosinase were almost equal. In addition, the inhibitory activities of the extracts on acetylcholinesterase (AChE) were stronger than the activity on butyrylcholinesterase (BChE). Molecular docking simulations revealed that luteolin 7-glucoside and apigenin 7-glucoside have particularly strong binding affinities against ChEs, tyrosinase, α-amylase and α-glucosidase when compared with co-crystallized inhibitors. Therefore, it was concluded that the compounds in question could act as effective inhibitors on cholinesterases, tyrosinase and digestive enzymes.     

Design,Synthesis, Molecular Docking,and Evaluation Antioxidant and Antimicrobial Activities for Novel 3-phenylimidazolidin-4-one and 2-aminothiazol-4-one Derivatives

On our way to discovering and developing compounds that have an antioxidant impact compared to ascorbic acid and other biological activities, we designed, synthesized, and evaluated a new series of heterocyclic moieties drugs (1–11) as antioxidants and antimicrobial agents. As starting moieties, these new candidates were derived from two promising heterocyclic compounds, imidazoldin-4-one and thiazol-4-one. Firstly, diphenylimidazol 1 was obtained because of the cyclo condensation one-pot ternary reaction of urea, aniline, and chloroacetic acid under thermal conditions. Out of this starting compound, we could design and create new vital rings such as purine and triazine as in compounds 5 and 6, respectively. Secondly, the start thiazole derivative 7 was obtained from the intermolecular cyclization of thiourea, chloroacetic acid, p-nitobezaldehyde in the presence of sodium acetate. We synthesized various derivatives from this second starting compound 7 by being subjected to different reagents such as aniline, phenylenediamine, phenylhydrazine, and barbituric acid to yield 8, 9, 10, and 11, respectively. Using ascorbic acid as the standard compound, the pharmacological testing for antioxidant activity assessment of the produced derivatives was evaluated against ABTS (2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid). Candidate 6 exhibited the best activity as an antioxidant agent compared to ascorbic acid as a reference compound. Moreover, all compounds were evaluated as antimicrobial agents against a series of bacteria and fungi. Among all synthesized compounds, compound 6 achieved high efficiency against two types of fungi and four kinds of bacteria, as Clotrimazole and Ampicillin were used as the reference agents, respectively. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopical and elemental investigations.     

Synthesis,Anticancer, Antioxidant,Anti-Inflammatory,Antimicrobial Activities,Molecular Docking,and DFT Studies of Sultams Derived from Saccharin

A series of N-substituted saccharins namely 2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetonitrile (2) and (alkyl 1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetate (3a–g) were synthesized, in moderate to excellent yields, from commercially available starting materials by two different approaches and their chemical structures were characterized by spectroscopic techniques (¹H-NMR, ¹³C-NMR, IR, and MS). All the synthesized compounds were evaluated for their anti-inflammatory toward IL-6 and TNF-α, antioxidant, as well as their anticancer activities against hepatic cancer cells. In addition, their anti-fungal and antibacterial activities against both Gram-positive and Gram-negative bacteria were tested. All the tested compounds have exhibited excellent (3a, d, e) to moderate anti-inflammatory activity. Additionally, esters (3b, f) and nitrile (2) showed excellent antioxidant activity. Furthermore, ester 3f, with isopropyl ester, exhibited the highest cytotoxic activity compared to the other esters. Moreover, all compounds were evaluated as selective inhibitors of the human COX-1 enzyme using molecular docking by calculating the free energy of binding, inhibition constant, and other parameters to find out the binding affinity. The molecular study showed that esters (3d, f) and nitrile (2) revealed the highest binding affinities, hence enhancing the inhibition activity with the active site of the COX-1 enzyme. All the tested compounds have more negative Gibbs free, electrostatic, and total intermolecular energies than the standard inhibitor ASA. These results indicate that, all the tested sultams are potent anti-inflammatory drugs as compared to standard inhibitors. Finally, the chemical properties and the quantum factors of synthesized sultams were calculated based on density functional theory (DFT) to predict reactivity, and then correlated with the experimental data. Ester 3f showed the lowest ionization potential and lowest energy gap (E_gap = 7.5691 eV), which was correlated with its cytotoxic activity. Furthermore, the spatial electron distribution of HOMO, LUMO were computed and it clearly indicates the electron donation ability of all the tested compounds.     

Wound Healing,Antimicrobial and Antioxidant Properties of Clinacanthus nutans (Burm.f.) Lindau and Strobilanthes crispus (L.) Blume Extracts

Clinacanthus nutans is known to be an anticancer and antiviral agent, and Strobilanthes crispus has proven to be an antidiuretic and antidiabetic agent. However, there is a high possibility that these plants possess multiple beneficial properties, such as antimicrobial and wound healing properties. This study aims to assess the wound healing, antioxidant, and antimicrobial properties of Clinacanthus nutans and Strobilanthes crispus. The Clinacanthus nutans and Strobilanthes crispus leaves were dried, ground, and extracted with ethanol, acetone, and chloroform through cold maceration. In a modified scratch assay with co-incubation of skin fibroblast and Methicillin-resistant Staphylococcus aureus, Clinacanthus nutans and Strobilanthes crispus extracts were assessed for their wound healing potential, and the antimicrobial activities of Clinacanthus nutans and Strobilanthes crispus extracts were performed on a panel of Gram-positive and Gram-negative bacteria on Mueller–Hinton agar based on a disc diffusion assay. To assess for antioxidant potential, 2,2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic and total flavonoid assays were conducted. In the modified scratch assay, Clinacanthus nutans extracts aided in the wound healing activity while in the presence of MRSA, and Strobilanthes crispus extracts were superior in antimicrobial and wound healing activities. In addition, Strobilanthes crispus extracts were superior to Clinacanthus nutans extracts against Pseudomonas aeruginosa on Mueller–Hinton agar. Acetone-extracted Clinacanthus nutans contained the highest level of antioxidant in comparison with other Clinacanthus nutans extracts.     

Synthesis,In Vitro Biological Evaluation and In Silico Molecular Docking Studies of Indole Based Thiadiazole Derivatives as Dual Inhibitor of Acetylcholinesterase and Butyrylchloinesterase

The current study was conducted to obtain hybrid analogues of indole-based thiadiazole derivatives (1–16) in which a number of reaction steps were involved. To examine their biological activity in the presence of the reference drug Donepezil (0.21 ± 0.12 and 0.30 ± 0.32 M, respectively), the inhibitory potentials of AChE and BuChE were determined for these compounds. Different substituted derivatives showing a varied range of inhibitory profiles, when compared to the reference drug, analogue 8 was shown to have potent activity, with IC50 values for AchE 0.15 ± 0.050 M and BuChE 0.20 ± 0.10, respectively, while other substituted compounds displayed good to moderate potentials. Varied spectroscopic techniques including ¹H, ¹³CNMR and HREI-MS were used to identify the basic skeleton of these compounds. Furthermore, all analogues have a known structure–activity relationship (SAR), and molecular docking investigations have verified the binding interactions of molecule to the active site of enzymes.     

Aphrodisiac Performance of Bioactive Compounds from Mimosa pudica Linn.: In Silico Molecular Docking and Dynamics Simulation Approach

Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Mimosa pudica Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research. The main goal of this study was to predict highly effective molecules from M. pudica Linn. for reaching and maintaining penile erection before and during sexual intercourse through in silico molecular docking and dynamics simulation tools. A total of 28 bioactive molecules were identified from this target plant through public repositories, and their chemical structures were drawn using Chemsketch software. Graph theoretical network principles were applied to identify the ideal target (phosphodiesterase type 5) and rebuild the network to visualize the responsible signaling genes, proteins, and enzymes. The 28 identified bioactive molecules were docked against the phosphodiesterase type 5 (PDE5) enzyme and compared with the standard PDE5 inhibitor (sildenafil). Pharmacokinetics (ADME), toxicity, and several physicochemical properties of bioactive molecules were assessed to confirm their drug-likeness property. Molecular dynamics (MD) simulation modeling was performed to investigate the stability of PDE5–ligand complexes. Four bioactive molecules (Bufadienolide (−12.30 kcal mol⁻¹), Stigmasterol (−11.40 kcal mol⁻¹), Isovitexin (−11.20 kcal mol⁻¹), and Apigetrin (−11.20 kcal mol⁻¹)) showed the top binding affinities with the PDE5 enzyme, much more powerful than the standard PDE5 inhibitor (−9.80 kcal mol⁻¹). The four top binding bioactive molecules were further validated for a stable binding affinity with the PDE5 enzyme and conformation during the MD simulation period as compared to the apoprotein and standard PDE5 inhibitor complexes. Further, the four top binding bioactive molecules demonstrated significant drug-likeness characteristics with lower toxicity profiles. According to the findings, the four top binding molecules may be used as potent and safe PDE5 inhibitors and could potentially be used in the treatment of ED.     

In Silico Study towards Repositioning of FDA-Approved Drug Candidates for Anticoronaviral Therapy: Molecular Docking,Molecular Dynamics and Binding Free Energy Calculations

The SARS-CoV-2 targets were evaluated for a set of FDA-approved drugs using a combination of drug repositioning and rigorous computational modeling methodologies such as molecular docking and molecular dynamics (MD) simulations followed by binding free energy calculations. Six FDA-approved drugs including, Ouabain, Digitoxin, Digoxin, Proscillaridin, Salinomycin and Niclosamide with promising anti-SARS-CoV-2 activity were screened in silico against four SARS-CoV-2 proteins—papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), SARS-CoV-2 main protease (Mpro), and adaptor-associated kinase 1 (AAK1)—in an attempt to define their promising targets. The applied computational techniques suggest that all the tested drugs exhibited excellent binding patterns with higher scores and stable complexes compared to the native protein cocrystallized inhibitors. Ouabain was suggested to act as a dual inhibitor for both PLpro and Mpro enzymes, while Digitoxin bonded perfectly to RdRp. In addition, Salinomycin targeted PLpro. Particularly, Niclosamide was found to target AAK1 with greater affinity compared to the reference drug. Our study provides comprehensive molecular-level insights for identifying or designing novel anti-COVID-19 drugs.     

Phytochemical Profiling,In Vitro Biological Activities,and In Silico Molecular Docking Studies of Dracaena reflexa

Dracaena reflexa, a traditionally significant medicinal plant, has not been extensively explored before for its phytochemical and biological potential. The present study was conducted to evaluate the bioactive phytochemicals and in vitro biological activities of D. reflexa, and perform in silico molecular docking validation of D. reflexa. The bioactive phytochemicals were assessed by preliminary phytochemical testing, total bioactive contents, and GC-MS analysis. For biological evaluation, the antioxidant (DPPH, ABTS, CUPRAC, and ABTS), antibacterial, thrombolytic, and enzyme inhibition (tyrosinase and cholinesterase enzymes) potential were determined. The highest level of total phenolic contents (92.72 ± 0.79 mg GAE/g extract) was found in the n-butanol fraction while the maximum total flavonoid content (110 ± 0.83 mg QE/g extract) was observed in methanolic extract. The results showed that n-butanol fraction exhibited very significant tyrosinase inhibition activity (73.46 ± 0.80) and acetylcholinesterase inhibition activity (64.06 ± 2.65%) as compared to other fractions and comparable to the standard compounds (kojic acid and galantamine). The methanolic extract was considered to have moderate butyrylcholinesterase inhibition activity (50.97 ± 063) as compared to the standard compound galantamine (53.671 ± 0.97%). The GC-MS analysis of the n-hexane fraction resulted in the tentative identification of 120 bioactive phytochemicals. Furthermore, the major compounds as identified by GC-MS were analyzed using in silico molecular docking studies to determine the binding affinity between the ligands and the enzymes (tyrosinase, acetylcholinesterase, and butyrylcholinesterase enzymes). The results of this study suggest that Dracaena reflexa has unquestionable pharmaceutical importance and it should be further explored for the isolation of secondary metabolites that can be employed for the treatment of different diseases.     

In Silico Molecular Docking and Simulation Studies of Protein HBx Involved in the Pathogenesis of Hepatitis B Virus-HBV

Current drug discovery involves finding leading drug candidates for further development. New scientific approaches include molecular docking, ADMET studies, and molecular dynamic simulation to determine targets and lead compounds. Hepatitis B is a disease of concern that is a life-threatening liver infection. The protein considered for the study was HBx. The hepatitis B X-interacting protein crystal structure was obtained from the PDB database (PDB ID-3MSH). Twenty ligands were chosen from the PubChem database for further in silico studies. The present study focused on in silico molecular docking studies using iGEMDOCK. The triethylene glycol monoethyl ether derivative showed an optimum binding affinity with the molecular target HBx, with a high negative affinity binding energy of −59.02 kcal/mol. Lipinski’s rule of five, Veber, and Ghose were followed in subsequent ADMET studies. Molecular dynamic simulation was performed to confirm the docking studies and to analyze the stability of the structure. In these respects, the triethylene glycol monoethyl ether derivative may be a promising molecule to prepare future hepatitis B drug candidates. Substantial research effort to find a promising drug for hepatitis B is warranted in the future.     

Chemical Analysis and Antimicrobial Activity of Moringa oleifera Lam. Leaves and Seeds

Moringa oleifera is a traditional food crop widespread in Asiatic, African, and South American continents. The plant, able to grow in harsh conditions, shows a high nutritional value and medicinal potential evidencing cardioprotective, anti-inflammatory, antioxidant, and antimicrobial properties. The purpose of this study was the phytochemical analysis of M. oleifera and the identification of the antimicrobial compounds by combining a chemical approach with in vitro tests. The metabolite profile of M. oleifera polar and apolar extracts of leaves and seeds were investigated by using Nuclear Magnetic Resonance spectroscopy and Gas Chromatography-Mass Spectrometry. The antimicrobial activity of all of the obtained extract was evaluated against four bacterial pathogens (Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Salmonella enterica). The chemical analysis provided a wide set of metabolites that were identified and quantified. Moreover, apolar extracts from seeds showed a significant concentration-dependent antimicrobial activity against S. aureus and S. epidermidis, (4 mg/mL reduced the viability up to 50%) that was associated to the content of specific fatty acids. Our results remarked the advantages of an integrated approach for the identification of plant metabolites and its use in association with biological tests to recognize the compounds responsible for bioactivity without compounds purification.     

Novel Galactopyranoside Esters: Synthesis,Mechanism, In Vitro Antimicrobial Evaluation and Molecular Docking Studies

One-step direct unimolar valeroylation of methyl α-D-galactopyranoside (MDG) mainly furnished the corresponding 6-O-valeroate. However, DMAP catalyzed a similar reaction that produced 2,6-di-O-valeroate and 6-O-valeroate, with the reactivity sequence as 6-OH > 2-OH > 3-OH,4-OH. To obtain novel antimicrobial agents, 6-O- and 2,6-di-O-valeroate were converted into several 2,3,4-tri-O- and 3,4-di-O-acyl esters, respectively, with other acylating agents in good yields. The PASS activity spectra along with in vitro antimicrobial evaluation clearly indicated that these MDG esters had better antifungal activities than antibacterial agents. To rationalize higher antifungal potentiality, molecular docking was conducted with sterol 14α-demethylase (PDB ID: 4UYL, Aspergillus fumigatus), which clearly supported the in vitro antifungal results. In particular, MDG ester 7–12 showed higher binding energy than the antifungal drug, fluconazole. Additionally, these compounds were found to have more promising binding energy with the SARS-CoV-2 main protease (6LU7) than tetracycline, fluconazole, and native inhibitor N3. Detailed investigation of Ki values, absorption, distribution, metabolism, excretion, and toxicity (ADMET), and the drug-likeness profile indicated that most of these compounds satisfy the drug-likeness evaluation, bioavailability, and safety tests, and hence, these synthetic novel MDG esters could be new antifungal and antiviral drugs.     

Antioxidant,Antimicrobial and Antitumor Studies of Transition Metal Complexes Derived from N-(2-Aminoethyl)-1,3-Propanediamine with DFT Calculations and Molecular Docking Investigation

New expected biologically active complexes for some of the first (Mn (II), Ni (II), Cu (II) and Zn (II)) and second (Rh (III) and Cd (II)) transitional metals rows with N-(2-Aminoethyl)-1,3-propanediamine as a ligand (AEPD)have been synthesized. All synthesized complexes were formed with 1:1 (metal: AEPD) stoichiometry except Ni (II) 1:2 (Ni: AEPD). The compounds were characterized by different analysis tools such as; elemental analysis, Fourier transform infrared (FTIR), ¹H-NMR, mass spectra, thermal analysis, electronic spectra, magnetic measurement and molar conductance techniques. AEPD ligand interacted with all metal ions as tridentate ligand by using the nitrogen atoms. On the other hand, density functional theory (DFT) calculations have been performed to confirm the optimized geometrical structures for both AEPD and its complexes. Furthermore, coordination compounds were screened for their potential antibacterial activities against six pathogenic bacteria as well as one kind of fungi in comparison to standard antibiotics by agar well diffusion method. The results show that most of the complexes exhibit antibacterial and antifungal activities against these organisms. Rh (III)-AEPD complex exhibited the strongest antibacterial effect followed by the Cd (II) complex but as antifungal agents Cd (II) was the first and the second was Rh (III). Also, the anticancer activity was screened for these metal complexes against growth of human liver cancer HEPG2 tumor cell line and this inhibition activity of Cd (II) chelate was noticed to be more active with lowest IC₅₀ than that of all other synthesized complexes. Unfortunately, Mn (II) and Rh (III) chelates lacked anticancer activity. The docking active sites interactions were evaluated using the selected protein for anticancer activity. Finally, antioxidant activity was studied. Mn (AEPD) showed maximum activity followed by complex of Rh (III).     

Design,Synthesis, Molecular Docking,and Tumor Resistance Reversal Activity Evaluation of Matrine Derivative with Thiophene Structure

Nasopharyngeal carcinoma (NPC) frequently occurs in Southern China. The main treatments of NPC are chemotherapy and radiotherapy. However, chemo-resistance arises as a big obstacle in treating NPC. Therefore, there is a great need to develop new compounds that could reverse tumor drug resistance. In this study, eight matrine derivatives containing thiophene group were designed and synthesized. Structures of these 8 compounds were characterized by ¹H-NMR, ¹³C-NMR, and high-resolution mass spectrometer (HRMS). The cytotoxicity and preliminary synergistic effects of these 8 compounds were detected against nasopharyngeal carcinoma (NPC) cells and cisplatin-resistant NPC cells (CNE2/CDDP), respectively. Furthermore, the in vivo and in vitro tumor resistance reversal effects of compound 3f were evaluated. Moreover, docking studies were performed in Bclw (2Y6W). The results displayed that compound 3f showed synergistic inhibitory effects with cisplatin against CNE2/CDDP cells proliferation via apoptosis induction. Docking results revealed that compound 3f may exert its effects via inhibiting anti-apoptosis protein Bcl-w.     

Antidiabetic Potential of Volatile Cinnamon Oil: A Review and Exploration of Mechanisms Using In Silico Molecular Docking Simulations

Cinnamon has been used as a flavoring and medicinal agent for centuries. Much research has focused on cinnamon bark powder, which contains antioxidants, flavonoids, carotenoids, vitamins, minerals, fiber, and small amounts of essential oil. However, isolated and concentrated cinnamon essential oil may also have important medicinal qualities, particularly in antidiabetic therapy. Some of the most common essential oil constituents identified in the literature include cinnamaldehyde, eugenol, and beta-caryophyllene. Due to their high concentration in cinnamon essential oil, these constituents are hypothesized to have the most significant physiological activity. Here, we present a brief review of literature on cinnamon oil and its constituents as they relate to glucose metabolism and diabetic pathogenesis. We also present molecular docking simulations of these cinnamon essential oil constituents (cinnamaldehyde, eugenol, beta-caryophyllene) that suggest interaction with several key enzymes in glucometabolic pathways.     

Antioxidant Activity Evaluation of FlexirubinType Pigment from Chryseobacterium artocarpi CECT 8497 and Related Docking Study

The current research is focused on studying the biological efficacy of flexirubin, a pigment extracted from Chryseobacterium artocarpi CECT 8497.Different methods such as DPPH, H₂O_2, NO^•, O₂^•−, ^•OH, lipid peroxidation inhibition by FTC and TBA, ferric reducing and ferrous chelating activity were carried out to evaluate the antioxidant activity of flexirubin. Molecular docking was also carried out, seeking the molecular interactions of flexirubin and a standard antioxidant compound with SOD enzyme to figure out the possible flexirubin activity mechanism. The new findings revealed that the highest level of flexirubin exhibited similar antioxidant activity as that of the standard compound according to the H₂O₂, ^•OH, O₂^•−, FTC and TBA methods. On the other hand, flexirubin at the highest level has shown lower antioxidant activity than the positive control according to the DPPH and NO• and even much lower when measured by the FRAP method. Molecular docking showed that the interaction of flexirubin was in the binding cavity of the SOD enzyme and did not affect its metal-binding site. These results revealed that flexirubin has antioxidant properties and can be a useful therapeutic compound in preventing or treating free radical-related diseases.     

A Comprehensive In Silico Exploration of Pharmacological Properties,Bioactivities, Molecular Docking,and Anticancer Potential of Vieloplain F from Xylopia vielana Targeting B-Raf Kinase

Compounds derived from plants have several anticancer properties. In the current study, one guaiane-type sesquiterpene dimer, vieloplain F, isolated from Xylopia vielana species, was tested against B-Raf kinase protein (PDB: 3OG7), a potent target for melanoma. A comprehensive in silico analysis was conducted in this research to understand the pharmacological properties of a compound encompassing absorption, distribution, metabolism, excretion, and toxicity (ADMET), bioactivity score predictions, and molecular docking. During ADMET estimations, the FDA-approved medicine vemurafenib was hepatotoxic, cytochrome-inhibiting, and non-cardiotoxic compared to the vieloplain F. The bioactivity scores of vieloplain F were active for nuclear receptor ligand and enzyme inhibitor. During molecular docking experiments, the compound vieloplain F has displayed a higher binding potential with −11.8 kcal/mol energy than control vemurafenib −10.2 kcal/mol. It was shown that intermolecular interaction with the B-Raf complex and the enzyme’s active gorge through hydrogen bonding and hydrophobic contacts was very accurate for the compound vieloplain F, which was then examined for MD simulations. In addition, simulations using MM-GBSA showed that vieloplain F had the greatest propensity to bind to active site residues. The vieloplain F has predominantly represented a more robust profile compared to control vemurafenib, and these results opened the road for vieloplain F for its utilization as a plausible anti-melanoma agent and anticancer drug in the next era.     

Novel Thiadiazole-Based Molecules as Promising Inhibitors of Black Fungi and Pathogenic Bacteria: In Vitro Antimicrobial Evaluation and Molecular Docking Studies

Novel 1,3,4-thiadiazole derivatives were synthesized through the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate and the appropriate hydrazonoyl halides in the presence of a few drops of diisopropylethylamine. The chemical structure of the newly fabricated compounds was inferred from their microanalytical and spectral data. With the increase in microbial diseases, fungi remain a devastating threat to human health because of the resistance of microorganisms to antifungal drugs. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) have higher mortality rates in many populations. The present study aimed to find new antifungal agents using the disc diffusion method, and minimal inhibitory concentration (MIC) values were estimated by the microdilution assay. An in vitro experiment of six synthesized chemical compounds exhibited antifungal activity against Rhizopus oryzae; compounds with an imidazole moiety, such as the compound 7, were documented to have energetic antibacterial, antifungal properties. As a result of these findings, this research suggests that the synthesized compounds could be an excellent choice for controlling black fungus diseases. Furthermore, a molecular docking study was achieved on the synthesized compounds, of which compounds 2, 6, and 7 showed the best interactions with the selected protein targets.