Semisynthetic Antimycobacterial C-3 Silicate and C-3/C-21 Ester Derivatives of Fusidic Acid: Pharmacological Evaluation and Stability Studies in Liver Microsomes, Rat Plasma, and Mycobacterium tuberculosis culture

AbstractAs a part of our systematic study of antimycobacterially active derivatives of salicylamides, a series of nineteen derivatives of N-(2-pyridylmethyl)salicylamides and N-(3-pyridylmethyl)salicylamides was synthesised. The compounds exhibited in vitro activity against Mycobacterium tuberculosis and M. avium. Their lipophilicity, R M, was measured by thin layer chromatography on silica gel impregnated with trioctadecylsilane and the logarithm of the partition coefficient (octanol-water), logP, was calculated. Both the parameters of lipophilicity correlated. The quantitative relationship between the structure and antimycobacterial activity was calculated. Antimycobacterial activity increased with an increase in lipophilicity. The N-(2-pyridylmethyl)salicylamide derivatives were more active than the derivatives of isomeric N-(3-pyridylmethyl)salicylamides. The geometry of compounds was calculated and the calculation was verified by measuring the length of the hydrogen bond between hydroxyl and carbonyl groups on the salicylic moiety.

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THE DESTRUCTION OF O,O-DIETHYL-S-2-DIETHYLAMINOETHYL PHOSPHOROTHIOLATE BY LIVER MICROSOMES

Canadian Journal of Biochemistry and Physiology ◽

10.1139/y59-030 ◽

1959 ◽

Vol 37 (1) ◽

pp. 297-305

Author(s):

J. F. Scaife ◽

D. H. Campbell

Keyword(s):

Guinea Pig ◽

Enzymatic Activity ◽

Inorganic Phosphate ◽

Enzyme System ◽

Liver Microsomes ◽

Rat Plasma ◽

Fresh Tissue ◽

Sh Groups ◽

Diisopropyl Phosphorofluoridate ◽

Liver Homogenates

Liver homogenates prepared from the rat, rabbit, mouse, and guinea pig possess an enzyme system capable of destroying O,O-diethyl-S-2-diethylaminoethyl phosphorothiolate at the rate of 150 to 200 μg/hr/g of fresh tissue. The homogenates prepared from the pig, dog, cow, and frog destroyed this compound at a rate of 50 to 100 μg/hr/g, but those prepared from man and the cat possessed negligible activity. Rat plasma, brain, kidney, diaphragm, whole gut, and spleen also possessed little or no activity. This enzyme system is located in the microsomes, disruption of which is accompanied by loss of enzymatic activity. The activity is dependent upon oxygen, inorganic phosphate, and diphosphopyridine nucleotide. Inhibitor studies indicate that enzymic SH-groups are necessary. The enzyme has no action on diisopropyl phosphorofluoridate, isosystox, or tetraethyl pyrophosphate, although these compounds are rapidly destroyed by the liver.

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Active Anti-Inflammatory and Hypolipidemic Derivatives of Lorazepam

Molecules ◽

10.3390/molecules24183277 ◽

2019 ◽

Vol 24 (18) ◽

pp. 3277

Author(s):

Panagiotis Theodosis-Nobelos ◽

Georgios Papagiouvannis ◽

Panos N. Kourounakis ◽

Eleni A. Rekka

Keyword(s):

Acute Inflammation ◽

Current Knowledge ◽

Rat Plasma ◽

Straightforward Method ◽

Inflammatory Drugs ◽

Multifunctional Agents ◽

Anti Inflammatory ◽

High Yields ◽

Derivatives Of ◽

And Oxidative Stress

Novel derivatives of some non steroidal anti-inflammatory drugs, as well as of the antioxidants α-lipoic acid, trolox and (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid with lorazepam were synthesised by a straightforward method at satisfactory to high yields (40%–93%). All the tested derivatives strongly decreased lipidemic indices in rat plasma after Triton induced hyperlipidaemia. They also reduced acute inflammation and a number of them demonstrated lipoxygenase inhibitory activity. Those compounds acquiring antioxidant moiety were inhibitors of lipid peroxidation and radical scavengers. Therefore, the synthesised compounds may add to the current knowledge about multifunctional agents acting against various disorders implicating inflammation, dyslipidaemia and oxidative stress.

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