C-3 Alkyl/Arylalkyl-2,3-dideoxy Hex-2-enopyranosides as Antitubercular Agents: Synthesis, Biological Evaluation, and QSAR Study

详细信息    查看全文

• 作者：Mohammad Saquib ; Manish K. Gupta ; Ram Sagar ; Yenamandra S. Prabhakar ; Arun K. Shaw ; Rishi Kumar ; Prakas R. Maulik ; Anil N. Gaikwad ; Sudhir Sinha ; Anil K. Srivastava ; Vinita Chaturvedi ; Ranjana Srivast
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：June 28, 2007
• 年：2007
• 卷：50
• 期：13
• 页码：2942 - 2950
• 全文大小：213K
• 年卷期：v.50,no.13(June 28, 2007)
• ISSN：1520-4804

文摘

A series of C-3 alkyl and arylalkyl 2,3-dideoxy hex-2-enopyranoside derivatives were synthesized by Morita-Baylis-Hillman reaction using enulosides 4, 5, and 6 and various aliphatic and aromatic aldehydes. Thecompounds were evaluated in vitro for the complete inhibition of growth of Mycobacterium tuberculosisH₃₇R_v. They exhibited moderate to good activity in the range of 25-1.56 g/mL. Among these, 4d, 4h, 5c,and 4hr showed activity at minimum inhibitory concentrations, 3.12, 6.25, 1.56, and 1.56 g/mL, respectively.These compounds were safe against cytotoxicity in VERO cell line and mouse macrophage cell line J 744A.1.A QSAR analysis by CP-MLR with alignment-free 3D-descriptors indicated the relevance of structure spacecomparable to the minimum energy conformation (from conformational analysis) of 5c to the activity. Thestudy indicates that the compounds attaining the conformational space of 5c and reflecting some symmetry,minimum eccentricity, and closely placed geometric and electronegativity centers therein are favorable foractivity.