Bekturov Institute of Chemical Sciences, Kazakhstan
Compounds that combine the piperidine structure with an aromatic amine group are known as hybrids of piperidine and aromatic amine. Research on these hybrids has been concentrated because of their possible medicinal uses. Piperidine-aromatic amine hybrids' characteristics are essential to their function in drug development, highlighting their significance in medicinal chemistry (1,2). Although many studies indicate the potential role of piperidine-aromatic amine hybrids in immunoregulation, the mechanism of their action and their effective role in various aspects of immune function require additional study.Throughout our study (3,4), series of piperidine-amine hybrids were described, which had high myelostimulating activity with piperazine and morpholine substituents at the nitrogen atoms of the bicyclic piperidine ring. Activity was lost when pyridine was used in place of the morpholine or piperazine ring in bicyclic piperidine. However, after acylation with O-benzoyl chloride N-pyridine substituted 3,7-diazabicyclo[3.3.1]nonane stimulated both erythro- and leukopoiesis while its N-piperazine analog stimulated only leukopoiesis. New compounds have been designed to see how increasing the aromatic rings affected the compounds' immunostimulatory properties. 1-(N-Alkoxyalkyl)-3,5-di(4-fluorobenzalidene)piperidon-4 containing piperidine-phenyl hybrids are obtained by reacting 1-(N-alkoxyalkyl)-4-oxopiperidine with 4-fluorobenzaldehyde in alkaline medium. To a suspension of 1 M of 1-(N-alkoxyalkyl)-3,5-di(4-fluorobenzalidene)piperidone-4 has been added 1 M of phenylhydrazine hydrochloride. All reactions were carried out in methanol. To obtain the inclusion complex of (E)-7-(4-fluorobenzylidene)-3-(4-fluorophenyl)-5-(N-alkoxyalkyl)-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridine hydrochlorides in ethyl alcohol have been mixed with an equimolar amount of b-cyclodextrin dissolved in distilled water. The resulting complex is an amorphous powder, melting above 240°С with decomposition. β-Cyclodextrin complexes hydrochlorides of pyrazolines have been studied for myelostimulating activity. The data were compared with methyluracil indicators.Compound 1 greatly accelerated the division of lymphocyte cells and the relative lymphocyte index reached the value of (93.99±1.9) %, the relative neutrophil and granulocyte-monocyte indices were critically low and amounted to (2.72±0.1) % and (3.44±0.1) % respectively. Administration group likewise had a successful restoration of platelet levels. Compared to the control group's value of 228.5±6.5)·109/L of blood, the total platelet index achieved a value of 548.0±32.41)·109/L of blood.Compound 2 efficiently induced leukocyte cell growth. The total leukocyte index was 2.11 times higher than the placebo group's blood (3.75±0.7)·109/L and marginally higher than the control group's (7.92±0.5) 109/L blood. The experimental group had a total platelet count of (477.50±21.05) 109/L of blood, which was 2.08 times greater than the control group. Compound 2 stimulated leukopoiesis at the level compared to methyluracil. It was distinguished by a pronounced stimulation of the lymphocyte pool with a pathological critical decrease in granulocytic-monocyte indicators.
Aigul has completed her PhD at the age of 30 years from Kazakh-British Technical University and postdoctoral studies from Birmingham University. She is the chief researcher of Laboratory of Chemistry of Synthetic and Natural Medicinal Substances, Bekturov Institute of Chemical Sciences. She has published more than 15 papers in reputed journals.