Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
Parasitol Res. 2013 Sep;112(9):3137-49. doi: 10.1007/s00436-013-3490-4. Epub 2013 Jun 22.
Schistosomiasis control is widely dependent on a single drug, praziquantel (PZQ). The potential for development of resistance to PZQ has justified the search for new alternative chemotherapies. In a previous study, we have been reported that three of 8-hydroxyquinoline derivatives namely: 3-((8-hydroxyquinolin-5-yl) sulfonyl) pentane-2,4-dione (HQSP), 5-((2,4-diphenyl-3H-benzo[b][1,4]diazepin-3-yl) sulfonyl) quinolin-8-ol (HQBD), and 5-((2,4-diphenyl-3H-pyrido[3,4-b][1,4] diazepin-3-yl) sulfonyl) quinolin-8-ol (HQPD) possess a potent anti-schistosomal activity in vitro. The aim of the present study was to evaluate the in vivo schistosomicidal effect of these three compounds on adult and immature worms of Schistosoma mansoni and their induced pathology. Treatment of S. mansoni-infected mice with 1000, 250, 150, and 200 mg/kg body weight of PZQ, HQSP, HQBD, and HQPD, respectively, reduced adult and immature worm burden by 94.63 and 31.32%, 73.63 and 5.45%, 76.5 and 28.11%, and 81.25 and 56.84%, respectively, compared to infected untreated mice. Moreover, numbers of egg per gram liver and intestine were decreased by 84 and 95.51%, 47.84 and 46.28 %, 53.18 and 59.37 %, and 54.22 and 67.26 as a result of PZQ, HQSP, HQBD, and HQPD treatment, respectively. Hepatic granuloma volume was also reduced by 40.10, 42.96, 35.72, and 72.09% due to PZQ, HQSP, HQBD, and HQPD treatment, respectively. In addition, hepatic histopathological alterations and collagen fiber deposition that accompanied with S. mansoni infection were largely retrieved with different treatments, especially HQPD treatment. Furthermore, humoral immune response, especially IgG response against S. mansoni antigens, was augmented with different treatments. This study concluded that among the three tested 8-hydroxyquinoline derivatives, HQPD is the most effective compound against adult and pre-mature worms of S. mansoni and can be used for the development of a new schistosomicidal drug.
血吸虫病控制广泛依赖于一种单一的药物，即吡喹酮（PZQ）。吡喹酮可能产生耐药性，这使得人们有理由寻找新的替代化学疗法。在之前的一项研究中，我们报告了 8-羟基喹啉衍生物中的三种，即 3-((8-羟基喹啉-5-基)磺酰基)戊烷-2,4-二酮（HQSP）、5-((2,4-二苯基-3H-苯并[b][1,4]二氮嗪-3-基)磺酰基)喹啉-8-醇（HQBD）和 5-((2,4-二苯基-3H-吡啶并[3,4-b][1,4]二氮嗪-3-基)磺酰基)喹啉-8-醇（HQPD），它们在体外具有很强的抗血吸虫活性。本研究的目的是评估这三种化合物对曼氏血吸虫成虫和未成熟虫体的体内杀血吸虫效果及其诱导的病理学变化。用 1000、250、150 和 200mg/kg 体重的 PZQ、HQSP、HQBD 和 HQPD 分别治疗感染曼氏血吸虫的小鼠，与未感染未治疗的小鼠相比，成虫和未成熟虫体的负荷分别减少了 94.63%和 31.32%、73.63%和 5.45%、76.5%和 28.11%、81.25%和 56.84%。此外，肝和肠内每克的虫卵数分别减少了 84%和 95.51%、47.84%和 46.28%、53.18%和 59.37%、54.22%和 67.26%，这是由于 PZQ、HQSP、HQBD 和 HQPD 的治疗。此外，由于 PZQ、HQSP、HQBD 和 HQPD 的治疗，肝肉芽肿体积分别减少了 40.10%、42.96%、35.72%和 72.09%。此外，肝组织病理学改变和胶原纤维沉积伴随着曼氏血吸虫感染，在不同的治疗下得到了很大的改善，特别是 HQPD 的治疗。此外，体液免疫反应，特别是针对曼氏血吸虫抗原的 IgG 反应，在不同的治疗下得到了增强。本研究得出结论，在所测试的三种 8-羟基喹啉衍生物中，HQPD 是对曼氏血吸虫成虫和未成熟虫体最有效的化合物，可用于开发新的杀血吸虫药物。
