Ultrasound-Assisted Extraction, Optimization, Phytochemical Screening and Analysis of Phenolics from Cycas Zeylanica and Antioxidant Activity Evaluation.

The present study focuses on investigating the phytochemical screening of indigenous species, C. zeylanica, for the first time. The leaf extracts have been prepared using ultrasound-assisted methods to obtain the best extraction results using different time and temperature conditions such as 30, 60, and 90 min. and 30, 40, and 60 °C, respectively. The results have been optimized using response surface methodology. Under the optimal extraction conditions of 60 °C for 43.57 minutes, an extract was produced with a yield of 0.238 g and a high total phenolic content of 181.1965 mg GAE/g. The total phenolic content has been evaluated and the presence of gallic acid has been confirmed through the HPLC technique. The optimal extract (OE) showed excellent antioxidant activity for the DPPH assay, with an IC50 of 3.1 µg/ml. Finally, GC-MS profiling has been done to screen the volatile component of the plant extract.

Synthesis, comparative in vitro antibacterial, antioxidant and UV fluorescence studies of bis indole Schiff bases and molecular docking with ct-DNA and SARS-CoV-2 Mpro.

In this study, synthesis of 15 novel bis indole-based Schiff bases (SBs) 4a-4o was conducted by condensation of 2-(1-aminobenzyl)benzimidazole with symmetrical bis-isatins linked via five alkyl chains (n = 2-6). These were subjected to ADME (absorption, distribution, metabolism and excretion), physiochemical properties, molecular docking, in vitro antibacterial and antioxidant studies. The in silico studies indicated lower toxicity with metabolic stability for nearly all the derivatives proving reliability as drug candidates. The comparative antibacterial study against Staphylococcus aureus and Escherichia coli, also showed a superior inhibition than reference drug and their mono counterparts. The increase in linker alkyl chain length and variation of substituents in indole, further predicted increased inhibition, with maximum value for compound 4o at 50 µg/ml. The in vitro calf thymus DNA (ct-DNA) binding ability of compounds 4c, 4f, 4i, 4l, 4 m, 4n, and 4o was evaluated via ultraviolet-visible and fluorescence spectroscopy techniques. A hyperchromic effect was observed with no apparent wavelength shift which predicted for the groove binding mode. A moderate binding constant for 4o, in fluorescence results, confirms groove binding. The molecular docking of 4o with ct-DNA (PDBID:1BNA) and SARS-CoV-2 Mpro (3CL protease, PDBID:6LU7) prove its efficacy as potential DNA binder and antiviral agent.

Hydrotrope assisted green synthesis of dicoumarols and in silico and in vitro antibacterial, antioxidant and xanthine oxidase inhibition studies.

Aqueous hydrotrope has been employed for the first time to synthesize heteroaryl dicoumarols by condensation of 4-hydroxycoumarin and different heterocyclic aldehydes. This method is highly efficient and green, and the same aqueous hydrotropic solution can be used up to five times without any considerable loss of yield in the product. The synthesized compounds showed good antibacterial potential against Gram-positive (Staphylococcus aureus/NTCC 0997 and B. oceanisediminis) and Gram-negative (Escherichia coli/D0157:H7 and E. coli rosetta) bacterial strains using the Resazurin microtiter plate visual method. The MIC value of 312 µg/ml for compounds 3b, 3k and 3l for S. aureus while 39 µg/ml for compounds 3a, 3b and 3k for E. coli and 625 µg/ml for 3a and 3b for B. oceanisediminis was observed. The compounds were screened via computational methods like molecular docking studies and molecular dynamic simulations with PDB Id's 2W9S and 2EX6. Antioxidant activity was assessed using DPPH and H2O2 assays. Five compounds with the best binding score in molecular docking with XO (PDB ID: 1FIQ) have been tested in an in-vitro study using an enzyme inhibition assay. Novel compound 3b gave the IC50 value of 0.28 µg/ml, comparable to the standard drug Allopurinol.Communicated by Ramaswamy H. Sarma.

A DFT study on substituents, solvent, and temperature effect and mechanism of Diels-Alder reaction of hexafluoro-2-butyne with furan.

CONTEXT: Furan and its derivatives constitute a vital class of heterocyclic chemistry used widely in organic synthesis via Diels-Alder reactions. As fluorine incorporation has been of great interest due to the limited possible pathways, the present study on [4 + 2] cycloaddition Diels-Alder reaction, between hexafluoro-2-butyne and 2-substituted (NH2, OCH3, OTMS, NHBoc) furans, uses the reaction as a likely route. The computational study revealed that that the reaction is feasible in all conditions and is most favorable for NH2 substituent in furan. The study of the effect of temperature has depicted that low temperature favors the formation of adducts, while the rise in temperature prefers ring opening to form 4-substituted-2,3-di(trifluoromethyl)phenol derivatives. The feasibility of a reaction has been determined by Gibbs energy change. The transition state study has been performed to find the activation energy, C-C single bond formation and global electron density transfer (GEDT) involved in the adduct formation. MEP plots have been used to understand the region of electrophilicity and nucleophilicity character. Furthermore, the mechanism for the formation of phenol products has been discussed. The decomposition of the NHBoc group at higher temperatures has been proved via a proposed mechanism and compared with experimental results. METHODS: The reaction was theoretically investigated using B3LYP hybrid functional with 6-311 + G(d,p) basis sets, in gas phase and under different solvent conditions like water, acetonitrile, and THF. The transition state structures of the adduct were optimized at the lower basis set B3LYP/6-31 + G(d,p) as well as at the higher basis set B3LYP/6-311 + G(d,p) level. The changes in Gibbs energy (∆G) for the formation of products at different temperatures and in various solvents have been calculated at B3LYP/6-311 + G(d,p) level.

An understanding of coronavirus and exploring the molecular dynamics simulations to find promising candidates against the Mpro of nCoV to combat the COVID-19: A systematic review.

The first infection case of new coronavirus was reported at the end of 2019 and after then, the cases are reported in all nations across the world in a very short period. Further, the regular news of mutations in the virus has made life restricted with appropriate behavior. To date, a new strain (Omicron and its new subvariant Omicron XE) has brought fear amongst us due to a higher trajectory of increase in the number of cases. The researchers thus started giving attention to this viral infection and discovering drug-like candidates to cure the infections. Finding a drug for any viral infection is not an easy task and takes plenty of time. Therefore, computational chemistry/bioinformatics is followed to get promising molecules against viral infection. Molecular dynamics (MD) simulations are being explored to get drug candidates in a short period. The molecules are screened via molecular docking, which provides preliminary information which can be further verified by molecular dynamics (MD) simulations. To understand the change in structure, MD simulations generated several trajectories such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, and radius of gyration for the main protease (Mpro) of the new coronavirus (nCoV) in the presence of small molecules. Additionally, change in free energy for the formation of complex of Mpro of nCoV with the small molecule can be determined by applying molecular mechanics with generalized born and surface area solvation (MM-GBSA). Thus, the promising molecules can be further explored for clinical trials to combat coronavirus disease-19 (COVID-19).

Design and synthesis of spiro[indole-thiazolidine]spiro[indole-pyrans] as antimicrobial agents.

A series of novel spiro[indole-thiazolidine]spiro[indole-pyran] derivatives were synthesized from N-(bromoalkyl)indol-2,3-diones via monospiro-bisindole intermediates; the two indole nuclei being connected via N-(CH(2))(n)-N linker. Synthesized compounds were evaluated for their antimicrobial activities in vitro against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, and Staphylococcus epidermis), four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumonia) as well as four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, and Candida albicans) using Cup plate method. Bis spiro-indoles exhibited stronger antibacterial and antifungal efficiency than their corresponding mono spiro-indoles. Compound 10e, the most active derivative was shown to inhibit the growth of all bacterial strains and two fungal strains (A. niger and C. albicans).

Spiro-Indole-Coumarin Hybrids: Synthesis, ADME, DFT, NBO Studies and In Silico Screening through Molecular Docking on DNA G-Quadruplex.

New series of hybrids were synthesized by combination of 4-hydroxycoumarin with spiro[indol-indazole-thiazolidine]-diones and spiro[indol-pyrazole-thiazolidine]-diones, via hitherto unknown Schiff bases. The effects of substituents, such as -F, -Br and -CH3, on the crucial characteristics pertaining to the hybrids were investigated through computational studies. In silico or virtual screening through molecular docking studies on the library of 22 compounds, including reference compounds, precursors, non-hybrid and hybrid derivatives, was performed on DNA G-quadruplex of the human genome. All six freshly synthesized hybrids showed high binding energy as compared to non-hybrids as well as reference compounds. The presence of substituents at 5-position of indole enhanced the binding tendency of the ligand. ADME studies indicated good oral bioavailability and absorption of these compounds. Density Functional Theory (DFT) calculations of hybrids were done at B3LYP/6-311G++(d,p) level of computation. Their HOMO and LUMO energy plots reflected the presence of high charge transfer and chemical potential. Natural bond order (NBO) calculations predicted hyperconjugative interactions. The Molecular Electrostatic Potential (MEP) surface plots showed possible electrophilic and nucleophilic attacking sites of the hybrids. Compound 10 a (5-fluoro-spiro[indol-indazole-thiazolidine]-dione-coumarin hybrid), on the basis of global reactivity descriptors, was filtered to be chemically most reactive with the highest binding energy of -8.23 kcal/mol with DNA G-quadruplex. The synthesized hybrid coumarin derivatives in correlation with theoretical docking studies validate that hybrid derivatives are more reactive compared to their non-hybrid counterparts.

Synthesis, DFT studies, molecular docking, antimicrobial screening and UV fluorescence studies on ct-DNA for novel Schiff bases of 2-(1-aminobenzyl) benzimidazole.

Novel Schiff bases (SBs) were synthesized by condensation of 2-(1-Amino benzyl) benzimidazole with heterocyclic and aromatic carbonyl compounds. The structural characterization was done using 1H, 13C NMR, FTIR and ES-MS spectroscopic techniques. The in silico pharmacokinetics showed that nearly all compounds obeyed Lipinski rule of 5 with low toxicity and metabolic stability. The global reactivity descriptors were calculated using DFT approach. The molecular docking result of SBs with ct-DNA suggested interaction via groove binding mode. The antibacterial activity was tested against S. aureus and E. coli, indicated significant inhibition than reference drug. The compound 4d gave best results at 50 µg ml-1 concentrations. UV/Vis and Fluorescence spectroscopy tools were used to evaluate ct-DNA binding ability of compounds 4a-e through hypochromic shift. The steady state fluorescence predicted a moderate binding constant of 1.12 × 104 for 4d, indicative of non-intercalative mode.

Protective effects of Aporosa octandra bark extract against D-galactose induced cognitive impairment and oxidative stress in mice.

Aporosa octandra (Buch.-Ham. ex D.Don) Vickery is a native species of India. Different parts of the plant are used for the medicinal purpose by the tribal peoples of south-eastern part of India. However, the biological properties of A. octandra have not been studied well. The extracts obtained from the bark of A. octandra were evaluated to determine their protective effect on cognitive impairment and oxidative stress in mice induced by D-galactose using the standard protocol. Different dosages of extract AOE-4 (100, 200, and 300 mg/kg, p.o.) were administered to mice, which were previously treated for six weeks with D-galactose (100 mg/kg s.c.). The D-galactose-induced mice showed significantly impaired cognitive behavior, i.e., oxidative defense, compared to the sham group. Six weeks of treatment with A. octandra extract AOE-4 (100, 200 and 300 mg/kg, p.o.) considerably improved the cognitive behavior and oxidative impairment of mice compared to the control alone (D-galactose). For the phytochemical investigation, the bark of A. octandra was successively extracted with dichloromethane and methanol. The chemical constituents of A. octandra were isolated by multiple column chromatography and characterized by different spectral analyses. (R)-Coclaurine (AO-5), an alkaloid, was isolated along with two other compounds from the AOE-4 extract; three more compounds were also isolated from the AOE-1 extract of the bark of A. octandra. All the compounds were isolated for the first time from the bark of A. octandra, and their structures were established by detailed spectral studies. The structure of compound AO-5 was also investigated and confirmed by X-ray diffraction and DFT studies. This study highlights the protective effect of A. octandra bark extract against D-galactose-induced biochemically dysfunction in mice. (R)-Coclaurine (AO-5) was isolated as one of the major components of A. octandra bark from AOE-4 extract; this compound could be further evaluated for the development of new potential drug candidates.