Programa de Pós-Graduação em Neurociências, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
J Pharm Pharmacol. 2021 Mar 27;73(5):673-681. doi: 10.1093/jpp/rgaa070.
While chronic feeding with high-fat or high-sugar diets is known related to obesity and type 2 diabetes, later data have indicated that it is also related to depression and anxiety appearance. In this regard, multi-target drugs raise considerable interest as promising therapeutic solutions to complex diseases. Considering the pharmacological effects of the imidazopyridine-derivative moiety imidazo[1,2-a]pyridine and the organoselenium molecules, the combination of both could be a feasible strategy to develop efficient drugs to handle obesity and related comorbidities, for example dyslipidemia and mood disorders.
The antidepressant- and anxiolytic-like properties of a selanylimidazopyridine compound, 2-Phenyl-3-(phenylselanyl)imidazo[1,2-a]pyridine (3-SePh-IP), were evaluated on high-fat/high-fructose diet (HFFD)-fed female Swiss mice.
Our results showed that a short-term HFFD (16 days) could promote a significant body weight gain, hypercholesterolemia, glucose intolerance, and anxiety- and depressive-like behaviour in mice. Concomitant treatment with 3-SePh-IP (10 mg/kg; i.p.) attenuated the HFFD-induced increase in cholesterol levels and blunted the anxiety- and depressive-like behaviour in mice.
3-SePh-IP holds multimodal pharmacological properties, which provide a rationale for further studies, for example to assess the underlying mechanisms linked to its anxiolytic- and antidepressive-like activities.
虽然长期高脂肪或高糖饮食与肥胖和 2 型糖尿病有关，但后来的数据表明，它也与抑郁和焦虑的出现有关。在这方面，多靶标药物作为治疗复杂疾病的有前途的治疗方法引起了相当大的兴趣。考虑到咪唑并吡啶衍生物咪唑并[1,2-a]吡啶和有机硒分子的药理学作用，将两者结合起来可能是开发有效药物来治疗肥胖症和相关合并症（例如血脂异常和情绪障碍）的可行策略。
在高脂肪/高果糖饮食（HFFD）喂养的雌性瑞士小鼠上评估了硒代咪唑并吡啶化合物 2-苯基-3-（苯基硒基）咪唑并[1,2-a]吡啶（3-SePh-IP）的抗抑郁和抗焦虑样特性。
我们的结果表明，短期 HFFD（16 天）可导致小鼠体重显著增加、胆固醇升高、葡萄糖不耐受以及焦虑和抑郁样行为。用 3-SePh-IP（10 mg/kg；腹腔注射）同时治疗可减轻 HFFD 引起的胆固醇水平升高，并减弱小鼠的焦虑和抑郁样行为。
3-SePh-IP 具有多模态的药理学特性，为进一步研究提供了依据，例如评估与其抗焦虑和抗抑郁样活性相关的潜在机制。
