C-3 alkyl/arylalkyl-2,3-dideoxy hex-2-enopyranosides as antitubercular agents: synthesis, biological evaluation, and QSAR study.
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. The compounds were evaluated in vitro for the complete inhibition of growth of Mycobacterium tuberculosis H37Rv. They exhibited moderate to good activity in the range of 25-1.56 mug/mL. Among these, 4d, 4h, 5c, and 4hr showed activity at minimum inhibitory concentrations, 3.12, 6.25, 1.56, and 1.56 mug/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 space comparable to the minimum energy conformation (from conformational analysis) of 5c to the activity. The study 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 for activity.
Saquib
Mohammad
M
Medicinal and Process Chemistry Division, Division of Molecular and Structural Biology, Drug Target Discovery and Development Division and Division of Microbiology, Central Drug Research Institute, Lucknow-226001, India.
Gupta
Manish K
MK
Sagar
Ram
R
Prabhakar
Yenamandra S
YS
Shaw
Arun K
AK
Kumar
Rishi
R
Maulik
Prakas R
PR
Gaikwad
Anil N
AN
Sinha
Sudhir
S
Srivastava
Anil K
AK
Chaturvedi
Vinita
V
Srivastava
Ranjana
R
Srivastava
Brahm S
BS
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D015169:Colony Count, Microbial; D018360:Crystallography, X-Ray; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship
D000995:Antitubercular Agents; D005960:Glucosides