Facile synthesis and stereochemical investigation of Mannich base derivatives: Evaluation of antioxidant property and antituberculostic potency

被引:20
|
作者
Parthiban, Paramasivam [1 ]
Subalakshmi, Viswalingam [2 ]
Balasubramanian, Krishnamurthy [3 ]
Islam, Md. Nurul [4 ]
Choi, Jae Sue [4 ]
Jeong, Yeon Tae [1 ]
机构
[1] Pukyong Natl Univ, Dept Image Sci & Engn, Pusan 608737, South Korea
[2] SASTRA Univ, Dept Biotechnol, Thirumalaisamudram 613401, Tamil Nadu, India
[3] AVVM Sri Pushpam Coll, Dept Bot & Microbiol, Poondi 613503, Tamil Nadu, India
[4] Pukyong Natl Univ, Dept Food Sci & Nutr, Pusan 608737, South Korea
关键词
Mannich base; 3-Azabicycle; Oxime ether; Stereochemistry; Antioxidant property; DPPH radical scavenging method; Antituberculostic activity; M. tuberculosis H(37)Rv; OXIME ETHERS; CHEMISTRY;
D O I
10.1016/j.bmcl.2011.02.103
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A mini-library of diversely substituted 2,4-diaryl-3-azabicycoinverted right perpendicular3.3.1inverted left perpendicularnonan-9-one O-methyloximes and their N-methyl analogs were synthesized by a non-laborious, modified and an optimized Mannich condensation in good yields. Both the ring N-methylation and oxime O-methylation were employed by various methods; of them, the usage of (BuOK)-Bu-t was found to be the superior in terms of good yield in short time. Stereochemistry of all the synthesized compounds was unambiguously established by their NMR spectral (H-1, C-13, H-1-H-1 COSY, H-1-C-13 one and multiple bond COSY and NOESY) as well as single-crystal XRD studies. Irrespective of the nature and position of the substituents, all the synthesized oxime ethers of the bicyclic Mannich bases as well as their N-methyl analogs adopted the twin-chair conformation with equatorial orientations of all the substituents. All the synthesized oxime ethers were evaluated for their antioxidant property by DPPH radical scavenging method. According to the structure-activity correlations, compound 4y was found to be a lead molecule with the IC50 of 0.187 mg/mL. Thus, the present study exploits the scope of finding more active analogs by further optimization with the incorporation of more electron enriched alkoxy/amino and/or phenolic groups on the heterocycle as well as oxime ether pharmacophore. Most of the synthesized molecules were screened for their antituberculostic potency against Mycobacterium tuberculosis H(37)Rv by zone of inhibition method. Of them, 4w/5d and 4x showed very promising inhibition zones of 21 and 23 mm, respectively, which leads to the optimization of 4x by introducing various substituents on the O-benzyl moiety to enhance the antituberculostic potency. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2287 / 2296
页数:10
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