Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives.

BACKGROUND: The search for pharmacologically effective agents among molecules bearing multiple functionalities is commonly practiced. In continuation of the search for new anti-malarial agents, new pyrazole-hydrazine coupled Schiff-base derivatives previously synthesized were screened for anti-malarial property. METHODS: Here, in vivo prophylactic and curative activities of the compounds were assessed while their binding affinity for falcipain-2, a crucial enzyme in Plasmodium survival, was done using computational techniques. RESULTS: The two derivatives (BepINH and BepBeH) respectively led to a significant (p < 0.05) reduction in parasitaemia count (0.76 ± 1.11 and 0.79 ± 1.19) at day 3 post-treatment relative to the negative control (16.37 ± 1.25). For the prophylactic study, it was observed that the highest parasitaemia suppression level of 95.35% and 95.17% for BepINH and BepBeH at 15 mg/kg was slightly comparable to that obtained for ACT-Lonart (99.38%). In addition, their haematological profiles indicate that they are potentially beneficial in suppressing haemolytic damage to RBC, thereby protecting the body against infection-induced anaemia. Docking calculations on the derivatives toward the Plasmodium falciparum falcipain-2 revealed that they favourably interacted with a binding affinity higher than that of a known cocrystallized inhibitor. CONCLUSION: This study confirms the relevance of multi-functional molecules in the search for new and effective anti-plasmodial agent and lay the foundation for further development of these compound series to potent anti-plasmodial agent that interacts with falcipain-2.

Monitoring of pesticide residues in fresh fruits and vegetables available in Nigerian markets and assessment of their associated health risks.

The presence of pesticide residues in agricultural products is posing serious health concerns for consumers. This study monitored the concentrations of pesticide residues in some selected fruit and vegetables, and their potential health risks were also assessed. Organochlorine (OCPs) and organophosphate (OPPs) residues were extracted and quantified with a gas chromatography-pulsed flame photometric detector. A total of 38 pesticide residues were identified and the results showed mean concentration (mg/kg fresh weight) of (OCPs) residues ranging from 0.02 to 0.37 and (OPPs) residues ranging from 0.01 to 0.33. The concentrations (mg/kg) of isodrin, heptachlor, dicofol, prothiophos, profenofos and dichlorvos were above the maximum residue limit. The non-carcinogenic health risk estimates revealed a possible potential health risk from consumption of the fruits and vegetables in adults and children for most of the pesticide residues. The cancer risk assessment estimates gave values below 10-6 which suggests no probable cancer risk. As a result of the increasing trend in pesticide use in Nigeria, routine monitoring of pesticide residues in agricultural produce is a necessity to ensure the safety of consumers.

Crystal structure, Hirshfeld surface and computational study of 1-(9,10-dioxo-9,10-di-hydroanthracen-1-yl)-3-propano-ylthio-urea.

The title compound, C18H14N2O3S, crystallizes in the ortho-rhom-bic crystal system and Pbca space group. The thio-urea chromophore is planar to an r.m.s deviation of 0.032 Šwith the thiol-ate sulfur atom being the most deviated. Bifurcated N-H⋯O intra-molecular hydrogen bonds result in an S(6) supra-molecular synthon. In the crystal, mol-ecules are linked by N-H⋯O inter-molecular hydrogen-bonding inter-actions and stabilized by C-H⋯π and π-π inter-actions. Hirshfeld surface analysis and fingerprint plot indicate the H⋯H inter-molecular contacts as the highest contributor to the overall surface contacts (38%) and this is supported by the high dispersive and electrostatic inter-action energies.

Periodicity of Single-Molecule Magnet Behaviour of Heterotetranuclear Lanthanide Complexes across the Lanthanide Series: A Compendium.

Acetato-bridged palladium-lanthanide tetranuclear heterometallic complexes of the form [Pd2 Ln2 (H2 O)2 (CH3 COO)10 ]⋅2 CH3 COOH [Ln2 =Ce2 (1), Pr2 (2), Nd2 (3), Sm2 (4), Tb2 (5), Dy2 (6), Dy0.2 Y1.8 (6''), Ho2 (7), Er2 (8), Er0.24 Y1.7 (8''), Tm2 (9), Yb2 (10), Y2 (11)] were synthesised and characterised by experimental and theoretical techniques. All complexes containing Kramers lanthanide ions [Ln3+ =Ce (1), Nd (3), Sm (4), Dy (6), DyY (6''), Er (8), ErY (8''), Yb (10)] showed field-induced slow magnetic relaxation, characteristic of single-molecule magnetism and purely of molecular origin. In contrast, all non-Kramers lanthanide ions [Ln3+ =Pr (2), Tb (5), Ho (7), Tm (9), Y3+ (11) is diamagnetic and non-lanthanide] did not show any slow magnetic relaxation. The variation in the electronic structure and accompanying consequences across the complexes representing all Kramers and non-Kramers lanthanide ions were investigated. The origin of the magnetic properties and the extent to which the axial donor-acceptor interaction involving the lanthanide ions and an electron-deficient d z 2 orbital of palladium affects the observed magnetic and electronic properties across the lanthanide series are presented. Unique consistent electronic and magnetic properties of isostructural complexes spanning the lanthanide series with properties dependent on whether the ions are Kramers or non-Kramers are reported.

Crystal structure and Hirshfeld surface analysis of a new di-thio-glycoluril: 1,4-bis-(4-meth-oxy-phen-yl)-3a-methyl-tetra-hydro-imidazo[4,5-d]imidazole-2,5(1H,3H)-di-thione.

In the title di-thio-glycoluril derivative, C19H20N4O3S2, there is a difference in the torsion angles between the thio-imidazole moiety and the meth-oxy-phenyl groups on either side of the mol-ecule [C-N-Car-Car = 116.9 (2) and -86.1 (3)°, respectively]. The N-C-N bond angle on one side of the di-thio-glycoluril moiety is slightly smaller compared to that on the opposite side, [110.9 (2)° cf. 112.0 (2)°], probably as a result of the steric effect of the methyl group. In the crystal, N-H⋯S hydrogen bonds link adjacent mol-ecules to form chains propagating along the c-axis direction. The chains are linked by C-H⋯S hydrogen bonds, forming layers parallel to the bc plane. The layers are then linked by C-H⋯π inter-actions, leading to the formation of a three-dimensional supra-molecular network. Hirshfeld surface analysis and two-dimensional fingerprint plots were used to investigate the mol-ecular inter-actions in the crystal.

Crystal structure of N'-[(1E)-1-(6-methyl-2,4-dioxo-3,4-di-hydro-2H-pyran-3-yl-idene)eth-yl]benzene-sulfono-hydrazide.

In the title compound, C14H14N2O5S, the mol-ecule exists in the enamine (C=C-NH) tautomeric form. The hydrazone fragment derived from the 3-acetyl-4-hy-droxy-6-methyl-2H-pyran-2-one moiety is approximately planar, with a maximum deviation of 0.1291 (11) Šfor the N atom bound to the S atom of the benzensulfono-hydrazide group. The latter adopts a gauche conformation relative to the hydrazone N-N bond, with an N-N-S angle of 113.54 (10)°. There is an intra-molecular N-H⋯O=C hydrogen bond that stabilizes the tautomeric form. In the crystal, mol-ecules are linked by N-H⋯O=C hydrogen bonds into chains extending parallel to [100].

Synthesis, Characterization, and Biological Activity of N (')-[(Z)-(3-Methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)(phenyl)methyl]benzohydrazide and Its Co(II), Ni(II), and Cu(II) Complexes.

Reaction of 1-phenyl-3-methyl-4-benzoyl-pyrazol-5-one and benzoyl hydrazide in refluxing ethanol gave N (')-[(Z)-(3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)(phenyl)methyl]benzohydrazide (HL(1)), which was characterized by NMR spectroscopy and single-crystal X-ray structure study. X-ray diffraction analyses of the crystals revealed a nonplanar molecule, existing in the keto-amine form, with intermolecular hydrogen bonding forming a seven-membered ring system. The reaction of HL(1) with Co(II), Ni(II), and Cu(II) halides gave the corresponding complexes, which were characterized by elemental analysis, molar conductance, magnetic measurements, and infrared and electronic spectral studies. The compounds were screened for their in vitro cytotoxic activity against HL-60 human promyelocytic leukemia cells and antimicrobial activity against some bacteria and yeasts. Results showed that the compounds are potent against HL-60 cells with the IC50 value ≤5 µM, while some of the compounds were active against few studied Gram-positive bacteria.

N'-[(4Z)-1-(3-Methyl-5-oxo-1-phenyl-4,5-di-hydro-1H-pyrazol-4-yl-idene)hex-yl]benzene-sulfono-hydrazide.

In the title compound, C22H26N4O3S, the dihedral angle between the pyrazoloneand phenyl rings is 21.73 (4)°. The benzensulfono-hydrazide group adopts a gauche conformation about the N-N vector. The C-N-N-S torsion angle is -109.88 (13)°. The mol-ecule exists as the enamine tautomeric form (C=C-NH). An intra-molecular N-H⋯O=C hydrogen bond occurs. In the crystal, mol-ecules are linked by pairs of N-H⋯O=C hydrogen bonds, forming centrosymmetric dimers.

N-(2-Chloro-eth-yl)morpholine-4-carbox-amide.

The title compound, C7H13ClN2O2, synthesized by the reaction of 2-chloro-ethyl iso-cyanate and morpholine, crystallizes with four molecules in the asymmetric unit, which have similar conformations and comprise two pairs each related by approximate non-crystallographic inversion centres. Two of them have a modest orientational disorder of the 2-chloro-ethyl fragments [occupancy ratio of 0.778 (4):0.222 (4)]. In the crystal, mol-ecules are linked by N-H⋯O=C hydrogen bonds, forming three crystallographically different kinds of infinite hydrogen-bonded chains extending along [001].