Pyrazolylphthalimide derivative
4
was synthesized and reacted with different reagents to afford the target compounds imidazopyrazoles
5-7
, pyrazolopyrimidines
9, 12, 14
and pyrazolotriazines
16, 17
containing phthalimide moiety. The prepared compounds were established by different spectral data and elemental analyses. Additionally, all synthesized derivatives were screened for their antibacterial activity against four types of Gram + ve and Gram-ve strains, and for antifungal activity against two fungi micro-organisms by well diffusion method. Moreover, the antiproliferative activity was tested for all compounds against human liver (HepG-2) cell line in comparison with the reference vinblastine. Moreover, drug-likeness and toxicity risk parameters of the newly synthesized compounds were calculated using
in silico
studies. The data from structure-actvity relationship (SAR) analysis suggested that phthalimide derivative bearing 3-aminopyrazolone moiety,
4
illustrated the best antimicrobial and antitumor activities and might be considered as a lead for further optimization. To investigate the mechanism of the antimicrobial and anticancer activities, enzymatic assay and molecular docking studies were carried out on
E. coli
topoisomerase II DNA gyrase B and VEGFR-2 enzymes.
Recently, herbal drugs and their bioactive compounds have gained popularity in the management of diabetes mellitus (DM), which has become an epidemic disease all over the world and is especially prevalent in the Kingdom of Saudi Arabia (KSA). This study aimed to investigate the antidiabetic effect of ethanolic and aqueous-ethanolic extracts of wild Ricinus communis (R. communis) leaves in streptozotocin (STZ) induced diabetic rats. Diabetic rats were administered orally with the mentioned extracts at doses of 300 and 600 mg/kg/BW for 14 days, and the obtained results of different biochemical parameters were compared with normal control, diabetic control and standard drug glibenclamide (5 mg/kg/BW). The obtained results revealed a remarkable and significantly (P < 0.05) reverse effect of the body weight loss, observed when diabetic rats were treated with ethanol and aqueous-ethanol extracts at 300 mg/kg/BW. Administration of the ethanol extract at 600 mg/kg/BW significantly (P < 0.05) reduced the blood glucose level. A significant increase in the AST, ALT and ALP levels (P < 0.05) was observed in the diabetic control and in the experimental groups with glibenclamide which was also significantly (P < 0.05) lowered after treatment with extracts at special doses. Total proteins, albumin, total bilirubin, direct bilirubin, creatinine and urea were also investigated and compared to the corresponding controls. We showed that administration of R. communis extract generally significantly (P < 0.05) ameliorated the biochemical parameters of diabetic rats. Also, the changes in serum electrolyte profile were assessed and the results demonstrate that administration of extracts at concentration of 600 mg/kg/BW generally inhibits the alteration maintain their levels. The obtained data imply the hypoglycemic effects of this plant, which may be used as a good alternative for managing DM and therefore validating its traditional usage in KSA.
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