Suthar Sharad Kumar, Bansal Sumit, Alam Md Maqusood, Jaiswal Varun, Tiwari Amit, Chaudhary Anil, Alex Angel Treasa, Joseph Alex
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal 576104, India.
Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 130701, Republic of Korea.
Bioorg Med Chem Lett. 2015 Nov 15;25(22):5281-5. doi: 10.1016/j.bmcl.2015.09.048. Epub 2015 Sep 21.
The 3-substituted oxindole derivatives were designed, synthesized, and evaluated for antidepressant activity by employing forced swimming test, tail suspension test, and MAO-A inhibition assay. Results of biological studies revealed that the majority of compounds exhibited potent to moderately potent activity and among them, 12 displayed potency comparable to that of the imipramine with %DID of 37.95 and 44.84 in the FST and TST, respectively. At the same time, imipramine showed %DID of 43.62 and 50.64 in the FST and TST, correspondingly. In the MAO-A inhibition assay, 12 showed an IC50 of 18.27 μmol, whereas the reference drug moclobemide displayed an IC50 of 13.1 μmol. The SAR study disclosed that the presence of bromo atom at the phenyl/furanyl or thienyl moiety in the oxindole derivatives was critical for the antidepressant activity.
通过强迫游泳试验、悬尾试验和单胺氧化酶A（MAO-A）抑制试验，设计、合成并评估了3-取代氧化吲哚衍生物的抗抑郁活性。生物学研究结果表明，大多数化合物表现出强效至中等强度的活性，其中12种化合物的活性与丙咪嗪相当，在强迫游泳试验和悬尾试验中的不动时间百分比（%DID）分别为37.95和44.84。同时，丙咪嗪在强迫游泳试验和悬尾试验中的%DID分别为43.62和50.64。在MAO-A抑制试验中，12表现出的半数抑制浓度（IC50）为18.27 μmol，而参比药物吗氯贝胺的IC50为13.1 μmol。构效关系研究表明，氧化吲哚衍生物中苯基/呋喃基或噻吩基部分存在溴原子对抗抑郁活性至关重要。
