Isoxazole analogues of dibenzazepine as possible leads against ulcers and skin disease: In vitro and in silico exploration.

Utilizing multi-target drugs shows great promise as an effective strategy against polygenic diseases characterized by intricate patho-mechanisms, such as ulcers, skin dermatitis, and cancers. The current research centers around the creation of hybrid compounds, connecting dibenzazepine and isoxazole, with the aim of exploring their potential as inhibitors for urease and tyrosinase enzymes. Analogs 6a, 6b, 6d, 6 h-6j, and 6 l demonstrated strong inhibitory potential against tyrosinase enzyme with IC50 values of 4.32 ± 0.31-12.36 ± 0.48. Whereas analogs 6a, 6c, 6e, 6f, 6h-6m, and 6r exhibited potent inhibitory activities against urease enzyme with IC50 values of 3.67 ± 0.91-15.60 ± 0.18 µM. Furthermore, compounds 6i, 6n, and 6r showed weak toxic effect in BJ-cell line, whereas the remaining compounds were found non-toxic to normal cell line. The mechanistic studies of potent inhibitors of both the enzymes showed competitive mode of inhibition. Molecular docking was employed to establish the relationship between structure and activity and to elucidate the interaction mechanism. This analysis revealed that the active analogs exhibited crucial interactions with the active site residues of urease and tyrosinase, thus corroborating our experimental results. Hence, the generated derivatives of dibenzazepine-linked isoxazoles present intriguing starting points for further investigations into their potential as inhibitors of urease and tyrosinase, with the potential for future modification and enhancement.

Effects of date fruit consumption on labour and vaginal delivery in Tabuk, KSA.

OBJECTIVES: The date fruit has been shown to possess several health benefits. This study aims to determine the effects of date fruit consumption on the onset and progression of labour. METHODS: A randomised controlled clinical study was conducted on 89 participants to assess the effects of date fruit consumption on the onset and progression of labour. Twenty-six participants consumed date fruits alone, and 32 consumed date fruits followed by drinking of water. Thirty-one served as controls. RESULTS: There was a significant positive impact of consuming (rutab) date fruits on maternal outcomes in both the first and third stages of labour (p < 0.05 and p < 0.001, respectively). In addition, there was a significant relationship with the foetal well-being factors, such as healthy liquor, foetal heart rate, presence of caput, and Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score at 5 min (p < 0.05). The other maternal and foetal well-being factors showed no significant relationship with consumption of date fruits during labour. CONCLUSION: The present study showed a promising effect of (rutab) date fruit consumption on the duration of the stages of labour. No significant differences were observed between the date fruit consumers and their counterparts regarding cervical dilatation; rupture of membranes; strength, frequency, and regularity of uterine contractions; tocometric reports; and maternal progression factors. Additionally, the APGAR score at 5 min was better among the infants whose mothers consumed date fruits.