Assessing the biological potential of new symmetrical ferrocene based bisthiourea analogues.

In the present work synthesis and characterization of five new bisferrocenyl bisthiourea analogues (G2M, S2M, G3F, G4F and T2M) is reported. UV-Visible and electrochemical studies were performed in order to have optical (absorption maximum, Molar absorption coefficient and optical band gap) and electrochemical parameters (Oxidation/reduction potentials and nature of the electrochemical process) of the compounds. In vitro various biological studies such as antibacterial, antifungal, anti-oxidant and antidiabetic activities were carried out to have comparative overview of the phermacochemical strength of the newly synthesized compounds. Similarly, theoretical analysis was accomplished utilizing density functional theory calculations. DFT/B3LYP (6-31G d, p) technique was used. With a view to explore the structure activity relationship (SAR) of the compounds theoretical docking analysis (against α-amylase, α-glucosidase) was also performed to have pictorial view and understanding of the actual interactions responsible for the activity. S2M displayed best antibacterial activity. Similarly, Antifungal and antidiabetic activities showed G3F as a best candidate, whereas T2M proved to be the best antioxidant agent.

Ultrafine α-CoOOH Nanorods Activated with Iron for Exceptional Oxygen Evolution Reaction.

Two-dimensional oxyhydroxide materials are proved to be a potential candidate for oxygen evolution reaction (OER). Robust, efficient, and cost-effective electrocatalysts are critical to overcome the sluggish kinetics and high overpotential of OERs. Herein, a simple co-precipitation method followed by solvothermal treatment is used to synthesize Fe-doped α-CoOOH at higher pH under optimum conditions for OER. The α-Fe0.24Co0.76OOH/NF illustrates superior OER electrocatalytic performance and requires an overpotential of only 280 mV to produce a current density of 50 mA cm-2 with excellent stability. The detailed analysis reveals that the exceptional OER performance originates from thin nanorods and partially due to the replacement of Fe in α-CoOOH. This work illustrates the presence of interlayer chloride ions through energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy.

i-Propylammonium Lead Chloride Based Perovskite Photocatalysts for Depolymerization of Lignin Under UV Light.

Lignin depolymerization for the purpose of synthesizing aromatic molecules is a growing focus of research to find alternative energy sources. In current studies, the photocatalytic depolymerization of lignin has been investigated by two new iso-propylamine-based lead chloride perovskite nanomaterials (SK9 and SK10), synthesized by the facile hydrothermal method. Characterization was done by Powder X-Ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), UV-Visible (UV-Vis), Photoluminescence (PL), and Fourier-Transform Infrared (FTIR) Spectroscopy and was used for the photocatalytic depolymerization of lignin under UV light. Lignin depolymerization was monitored by taking absorption spectra and catalytic paths studied by applying kinetic models. The %depolymerization was calculated for factors such as catalyst dose variation, initial concentration of lignin, and varying temperatures. Pseudo-second order was the best suited kinetic model, exhibiting a mechanism for lignin depolymerization that was chemically rate controlled. The activation energy (Ea) for the depolymerization reaction was found to be 15 kJ/mol, which is remarkably less than conventional depolymerization of the lignin, i.e., 59.75 kJ/mol, exhibiting significant catalytic efficiencies of synthesized perovskites. Products of lignin depolymerization obtained after photocatalytic activity at room temperature (20 °C) and at 90 °C were characterized by GC-MS analysis, indicating an increase in catalytic lignin depolymerization structural subunits into small monomeric functionalities at higher temperatures. Specifically, 2-methoxy-4-methylphenol (39%), benzene (17%), phenol (10%) and catechol (7%) were detected by GC-MS analysis of lignin depolymerization products.

In silico and in vivo investigation of ferrocene-incorporated acyl ureas and homoleptic cadmium carboxylate derivatives for anticonvulsant, anxiolytic, and sedative potential.

In this study different derivatives of ferrocene-incorporated acyl ureas and homoleptic cadmium carboxylates were investigated for potential anticonvulsant, anxiolytic and sedative properties, using in-silico and in-vivo techniques. The molecular docking studies reveled that ferrocene compounds derivative 1-(4-bromobenzoyl)-3-(4-ferrocenylphenyl) urea (PB1) and cadmium compounds derivative bis (diphenylacetato) cadmium (II) (DPAA) exhibit binding affinities against various neurotherapeutic molecular targets involved in epilepsy, anxiety, and sedation. Both PB1 and DPAA showed high binding affinities against protein targets like mammalian shaker voltage dependent potassium channel beta subunit complex, calcium release-activated calcium channel, sodium channel 2A inactivation gate, human sodium/hydrogen exchanger regulatory factor, and gamma amino butyric acid A receptor associated protein. PB1 (2-10 mg/kg) and DPAA (1-5 mg/kg) delayed onset time of pentylenetetrazole-induced myoclonic jerks and tonic-clonic seizures in mice while decreased duration of tonic-clonic seizures, determining the anticonvulsant effect of these compounds. PB1 and DPAA (0.5-1 mg/kg) exhibited anxiolytic effect by increasing time spent and number of animals entries into open arms, while decreasing time spent in dark compartment. Furthermore, PB1 (0.5-1 mg/kg) and DPAA (0.1-1 mg/kg) reduced onset time of sleep and increased duration time of sleep in mice, showing sedative effect. Taken together, our results indicate that aforementioned derivatives of ferrocene and cadmium are potent neurotherapeutic agents possessing anticonvulsant, anxiolytic and sedative properties.

Facile synthesis of fluoro, methoxy, and methyl substituted ferrocene-based urea complexes as potential therapeutic agents.

In the present work, the synthesis, characterization (FT-IR, multinuclear (1H and 13C) NMR, AAS, Raman, and elemental analysis), DNA binding (cyclic voltammetry, UV-Vis spectroscopy and viscometry), and in vitro biological assessment of nine new ferrocene-based ureas are reported. The desulphurization of ferrocenyl thioureas to the corresponding oxo analogues using aqueous sodium hydroxide and mercuric chloride led to the ferrocenyl ureas (F1-F9) in high yields. The DNA binding studies performed by cyclic voltammetry and UV-Vis spectroscopy produced results that are in close agreement with one another for the binding constants (K) and an electrostatic mode of interaction was observed. The nature and the extent of interaction with DNA was further investigated by viscometry. The DFT/B3LYP method was used to determine the charge distribution and HOMO/LUMO energies of the optimized structure. The DFT calculated HOMO and LUMO energies correlate well with the experimentally determined redox potential values. The synthesized ferrocenyl derivatives exhibited good scavenging activity against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). These complexes were also scanned for their in vitro cytotoxicity against human carcinoma cell line THP-1 (leukemia cells). The results showed a moderate level of cytotoxicity against the subjected cancer cell line as compared with the standard chemotherapeutic drug (cisplatin).

Solution-phase microwave assisted parallel synthesis, biological evaluation and in silico docking studies of N,N'-disubstituted thioureas derived from 3-chlorobenzoic acid.

A facile and robust microwave-assisted solution phase parallel synthesis protocol was exercised for the development of a 38-member library of N,N'-disubstituted thiourea analogues (1-38) by using an identical set of conditions. The reaction time for synthesis of N,N'-disubstituted thiourea analogues was drastically reduced from a reported duration of 8-12h for conventional methods to only 1.5-2.0min. All the derivatives (1-38) were characterized by physico-analytical techniques such as elemental analysis in combination with FT-IR, (1)H, (13)C NMR and by single crystal XRD analysis have also been performed. These compounds were screened for their in vitro urease inhibition activities. Majority of compounds exhibited potent urease inhibition activities, however, the most significant activity was found for 16, with an IC50 value of 1.23±0.1µM. Furthermore, the synthesized compounds were screened for their cytotoxic potential against lungs cancer cell lines. Cell culture studies demonstrated significant toxicity of the compounds on the cell lines, and the levels of toxicity were altered in the presence of various side groups. The molecular docking studies of the most potent inhibitors were performed to identify the probable binding modes in the active site of the urease enzymes. These compounds have a great potential and significance for further investigations.

Antileishmanial, DNA Interaction, and Docking Studies of Some Ferrocene-Based Heteroleptic Pentavalent Antimonials.

A series of ferrocenyl pentavalent antimonials (1-8) were synthesized and characterized by elemental analysis, FT-IR, and multinuclear ((1) H and (13) C) NMR spectroscopy. These antimonials were evaluated for their antileishmanial potential against Leishmania tropica KWH23, and by biocompatibility and membrane permeability assays. Moreover, mechanistic studies were carried out, mediated by DNA targeting followed by computational docking of ferrocenyl antimonials against the leishmanial trypanothione reductase enzyme. It was observed that the antimonials 1-8 were 390-fold more efficacious (IC50 ) as compared with the standard antimonial drug used. Cytotoxicity results showed that these antimonials are highly active even at low concentrations and are biocompatible with human macrophages. Antimonials 1-8 exhibited extensive intercalation with DNA and, furthermore, docking interactions highlighted the potential interactive binding of the anitimonials within the trypanothione reductase active site, with van der Waals interactions contributing significantly to the process. Hence, it is suggested that the reported antimonials demonstrate high efficacy, less toxicity, and target multiple sites of the Leishmania parasite.

Synthesis, characterization and urease inhibition, in vitro anticancer and antileishmanial studies of Ni(II) complexes with N,N,N'-trisubstituted thioureas.

A series of N,N,N'-trisubstituted thioureas (1-12) and their Ni(II) complexes (1a-12a) were synthesized and characterized by multinuclear ((1)H and (13)C) NMR, FT-IR spectroscopy and LC-MS techniques in combination with elemental analysis. The crystal structures of both ligands and Ni(II) chelates of type Ni(L-O, S)2 were determined by single crystal X-ray diffraction analysis. All the complexes were adopted to have square planar geometry, where the N,N,N'-trisubstituted thioureas showed bidentate mode of coordination at nickel centre through oxygen and sulfur atoms. The synthesized complexes were screened for potential inhibitors of Jack bean urease. Compounds 1a and 3a were observed as most potent inhibitors of urease exhibiting IC50 values of 1.17 ± 0.12 and 1.19 ± 0.41 µM, respectively. Cytotoxicity assay on lung carcinoma (H-157) and kidney fibroblast (BHK-21) cell showed that compounds were significant anticancer agents. Additionally, the complexes were tested against Leishmania major and found to be potent antileishmanial agents.

Guanidines from 'toxic substances' to compounds with multiple biological applications--detailed outlook on synthetic procedures employed for the synthesis of guanidines.

Guanidines to begin with, were thought of being harmful substances associated with medical ailment. With the advent of World War I and the impact it left on the populations at large research focus was shifted, towards polymer synthesis and that too on plastics and rubbers which were mostly employed in various artillery equipments. In the surge, to get plastics and rubbers with enhanced mechanical properties, many variedly substituted guanidines used as accelerators in vulcanization of polymers were synthesized using different procedures. Continuous research on guanidines, led scientists to develop different protocols and routes for the synthesis of these compounds, later these were tested for their possible use in various areas and now these are sought for their enhanced biomedical and catalytic applications. This review article presents thirty six different synthetic procedures employed for the synthesis of guanidines over the years including seventy schemes and a brief account on the reported wide ranging applications of some novel guanidines.

Microdiplanol and microdiplane: a new m-anisaldehyde and a new 24-methylcholestanol derivative from the endophytic fungus Microdiplodia sp.

Phytochemical investigation of the endophytic fungus Microdiplodia sp. afforded a new m-anisaldehyde derivative named microdiplanol (1) and a new 24-methylcholestanol derivative named microdiplane (2). Their structures were confirmed by a comprehensive analysis of 1D and 2D NMR and mass spectrometric data.

Synthesis, chemical characterization, DNA binding, antioxidant, antibacterial, and antifungal activities of ferrocence incorporated selenoureas.

Ferrocene-incorporated selenoureas 1-(4-methoxybenzoyl)-3-(4-ferrocenylphenyl)selenourea (P4Me), 1-(3-methoxybenzoyl)-3-(4-ferrocenylphenyl)selenourea (P3Me), and 1-(2-methoxybenzoyl)-3-(4-ferrocenylphenyl)selenourea (P2Me) were synthesized and characterized by nuclear magnetic resonance, Fourier transform infrared spectroscopy, atomic absorption spectroscopy, CHNS, and single-crystal X-ray diffraction. DNA interaction of the compounds was investigated with cyclic voltammetry, UV-visible spectroscopy, and viscometry, which is a prerequisite for anticancer agents. Drug-DNA binding constant was found to vary in the sequence: K(P4Me) (4.9000 × 104 M⁻¹) > K(P2Me) (2.318 × 104 M⁻¹) > K(P3Me) (1.296 × 104 M⁻¹). Antioxidant (1,1-diphenyl-2-picrylhydrazyl), antifungal (against Faussarium solani and Helmentosporium sativum), and antibacterial (against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis) activities have also been reported in addition.

Coniothyren: a new phenoxyphenyl ether from the endophytic fungus, Coniothyrium sp.

Phytochemical investigation of the endophytic fungus Coniothyrium sp. resulted in the isolation of a new phenoxyphenyl ether, named coniothyren (1), and two known compounds, coniol (2) and (+)-epoxydon (3). The structure of the new compound was elucidated by detailed spectroscopic analysis, namely, (1)H NMR, (13)C NMR, COSY, HMQC, HMBC, and HR-EI-MS. Preliminary studies demonstrated that (+)-epoxydon (3) displayed good antibacterial and antialgal activities toward Bacillus megaterium and Chlorella fusca, respectively.

In vivo effects of a selected thiourea derivative 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) against nociception, inflammation and gastric ulcerogenicity: Biochemical, histopathological and in silico approaches.

The current study was designed to investigate the potential of a synthetic therapeutic agent for better management of pain and inflammation, exhibiting minimal to non-existent ulcerogenic effects. The effect of 1-(2-chlorobenzoyl)-3-(2,3-dichlorophenyl) thiourea was assessed through model systems of nociception and anti-inflammatory activities in mice. In addition, the ulcerogenic potential was evaluated in rats using the NSAID-induced pyloric ligation model, followed by histopathological and biochemical analysis. The test was conducted on eight groups of albino rats, comprising of group I (normal saline), groups II and III (aspirin® at doses of 100 mg/kg and 150 mg/kg, respectively), groups IV and V (indomethacin at doses of 100 mg/kg and 150 mg/kg, respectively), and groups VI, VII, and VIII (lead-compound at 15 mg/kg, 30 mg/kg and 45 mg/kg doses, respectively). Furthermore, molecular docking analyses were performed to predict potential molecular target site interactions. The results showed that the lead-compound, administered at doses of 15, 30, and 45 mg/kg, yielded significant reductions in chemically and thermally induced nociceptive pain, aligning with the levels observed for aspirin® and tramadol. The compound also effectively suppressed inflammatory response in the carrageenan-induced paw edema model. As for the ulcerogenic effects, the compound groups displayed no considerable alterations compared to the aspirin® and indomethacin groups, which displayed substantial increases in ulcer scores, total acidity, free acidity, and gastric juice volume, and a decrease in gastric juice pH. In conclusion, these findings suggest that our test compound exhibits potent antinociceptive, anti-inflammatory properties and is devoid of ulcerogenic effects.

The genus Pluchea: phytochemistry, traditional uses, and biological activities.

In this review, literature data on phytochemical and biological investigations on the genus Pluchea are compiled. Pluchea is a genus of flowering plants in the Asteraceae family and comprises ca. 80 species distributed mainly in Northern and Southern America, Africa, Asia, and Australia. Sesquiterpenoids and flavonoids are the main constituents of this genus. Compounds isolated from plants of the Pluchea genus display a variety of biological properties, viz., anticancer, antileishmanial, immunosuppressive, antioxidant, anti-acetylcholinesterase, antimicrobial, trypanocidal, hepatoprotective, cytotoxic, larvicidal, anti-ulcer, anti-inflammatory, and antinociceptive activities.

Antitumor, antioxidant and antimicrobial studies of substituted pyridylguanidines.

A series of N-pivaloyl-N'-(alkyl/aryl)-N''-pyridylguanidine of general formula C4H9CONHC(NR¹R²)NPy have been synthesized and characterized using elemental analysis, FT-IR, multinuclear NMR spectroscopy, and in the case of compounds 7 and 11, by single crystal X-ray diffraction (XRD). The synthesized guanidines were tested for antitumor activities against potato tumor, and showed excellent inhibition against Agrobacterium tumefaciens (AT10)-induced tumor. The antioxidant and antimicrobial activities of these new compounds against various bacterial and fungal strains were also investigated.

1-(2-Chloro-benzo-yl)-3-(2-trifluoro-methyl-phen-yl)thio-urea.

The dihedral angle between the benzene rings in the title compound, C15H10ClF3N2OS, is 54.02 (4)°. An intra-molecular N-H⋯O hydrogen bond occurs. In the crystal, N-H⋯S hydrogen bonds link the mol-ecules into inversion dimers.

1-(2-Chloro-benzo-yl)-3-(3-meth-oxy-phen-yl)thio-urea.

The title compound, C15H13ClN2O2S, exists in the solid state in its thione form with typical thio-urea C-S and C-O bonds lengths as well as shortened C-N bonds. An intra-molecular N-H⋯O hydrogen bond stabilizes the mol-ecular conformation. In the crystal, N-H⋯S hydrogen bonds link the mol-ecules into centrosymmetric dimers.

1-(2-Chloro-benzo-yl)-3-(pyrimidin-2-yl)thio-urea.

In the title compound, C12H9ClN4OS, the carbonyl group is at a cis position with respect to the thio-urea unit. The dihedral angle between the phenyl and pyrimidine ring is 16.49 (6)°. An intra-molecular N-H⋯N hydrogen bond stabilizes the mol-ec-ular conformation. In the crystal, N-H⋯N, C-H⋯O and C-H⋯S hydrogen bonds generate chains along the bc axis.

2-(3-Chloro-benzo-yl)-3-(3,4-di-chloro-phen-yl)-1-(4-ferrocenylphen-yl)guanidine.

In the title compound, [Fe(C5H5)(C25H17Cl3N3O)], the isolated cyclo-penta-dienyl (Cp) ring is disordered over two set of sites in a 0.577 (8):0.423 (8) ratio. The dihedral angle between the other Cp ring and its attached benzene ring is 13.6 (3)°, and that between the benzene ring and the guanidine group is 64.8 (2)°. One of the N-H groups forms both an intra- and an inter-molecular N-H⋯O hydrogen bond; the other N-H group does not form any hydrogen bonds. In the crystal, pairs of the inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into inversion dimers.

New ferrocene integrated amphiphilic guanidines: Synthesis, spectroscopic elucidation, DFT calculation and in vitro α-amylase and α-glucosidase inhibition combined with molecular docking approach.

Three N, N', N″-trisubstituted ferrocenyl guanidines (MG-10, MG-12 and MG-14) were synthesized, characterized by several analytical methods such as FT-IR, 1H and 13C NMR, elemental analysis and UV-visible spectroscopy. These compounds have long chain aliphatic groups therefore their aliphatic nature has been evaluated by determining their critical micelle concentration (CMC). CMC point decreases from 0.036 mM to 0.013 mM with increase in the aliphatic chain length. The quantum mechanical parameters such as the energy of frontier molecular orbitals (EHOMO and ELUMO) and the Mulliken charge distribution on the optimized structures were determined using a DFT/B3LYP method combined with the 6-31G (d,p) basis set in the gas phase. The in vitro antidiabetic activity of synthesized compounds showed that MG-12 has IC50value 23.10 µg/mL against α-amylase while MG-10 has IC50value 27.32 µg/mL against α-glucosidase with the respective standard Acarbose (IC50value 20.12 µg/mL). Theoretical docking analysis demonstrated that MG-10 and MG-12 interacted with α-amylase by 3 types of interaction, including hydrogen bonds, hydrophobic interactions and electrostatic interactions.