Synthesis and anti-inflammatory activity evaluation of novel chroman derivatives

In an effort to develop potent anti-inflammatory agents, a series of novel chroman derivatives including acyclic amidochromans, chromanyl esters and chromanyl acrylates have been designed, synthesized and fully characterized. These chroman analogues were screened for their anti-inflammatory activities through inhibition of the TNF-α-induced ICAM-1 expression on human endothelial cells. A structure-activity relationship was also established and it has been found that in the case of carboxy chromans and amidochromans, the chain length of the amide moiety, branching of the side chain and the presence of the substituents on the phenyl ring have significant effects on their inhibitory activities, while in chromanyl acrylates, the number of methoxy groups, their relative positions on the phenyl ring, and presence of functional groups in the α,β-unsaturated ester moiety played a critical role on their activities. Compound 14 (N-hexyl-7-hydroxy-2,2-dimethylchromane-6-carboxamide) was found to be the most potent compound in inhibiting the TNF-α-induced expression of ICAM-1 on endothelial cells. This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

Authors
Matta A.1 , Sharma A.K.1, 2 , Tomar S.1 , Cao P.1 , Kumar S.1 , Balwani S.3 , Ghosh B.3 , Prasad A.K.1 , Van Der Eycken E.V. , Depass A.L.5 , Wengel J.6 , Parmar V.S.1, 2, 6, 7 , Len C.8 , Singh B.K.1, 2
Journal
New Journal of Chemistry
Publisher
Royal Society of Chemistry
Number of issue
32
Language
English
Pages
13716-13727
Status
Published
Link
External link
DOI
10.1039/d0nj02125c
Volume
44
Year
2020
Organizations
  • 1 Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi, 110 007, India
  • 2 Laboratory for Organic and Microwave-Assisted Chemistry (LOMAC), Department of Chemistry, University of Leuven, Celestijnenlaan 200F, Leuven, B-3001, Belgium
  • 3 Molecular Immunogenetics Lab, Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (CSIR-IGIB), Mall Road, Delhi, 110 007, India
  • 4 Peoples' Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, Moscow, 117198, Russian Federation
  • 5 Department of Biology, Long Island University, One University Plaza, Brooklyn, NY 11201, United States
  • 6 Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, Odense M, DK 5230, Denmark
  • 7 Department of Chemistry and Environmental Science, Medgar Evers College, City University of New York, 1638 Bedford Avenue, Brooklyn, NY 11225, United States
  • 8 Chimie ParisTech, Psl University, Cnrs, Institute of Chemistry for Life and Health Sciences-i-CLeHS, 11 rue Pierre et Marie Curie, Paris, F-75005, France
Keywords
Amides; Endothelial cells; Salts; Anti-inflammatory activity; Anti-inflammatory agents; Chroman derivatives; Human endothelial cells; Inhibitory activity; Relative positions; Structure activity relationships; Unsaturated esters; Esters; 2,2 dimethyl n pentylchroman 6 carboxamide; 3 [2,2 dimethyl 3,4 dihydro (2h)benzopyran 6yl] 2e propenoic acid; 5,7 dihydroxy 2,2 dimethylchroman; 5,7 dimethoxy 2,2 dimethylchroman 8 carbaldehyde; 6 formyl 2,2 dimethyl 3,4 dihydro (2h)benzopyran; 7 hydroxy 2,2 dimethyl n pentylchroman 6 carboxamide; 7 methoxy 2,2 dimethylchroman; 7 methoxy 2,2 dimethylchroman 6 carbaldehyde; 7,8 dihydroxy 2,2 dimethylchroman; 7,8 dimethoxy 2,2 dimethylchroman 6 carbaldehyde; antiinflammatory agent; chroman derivative; methyl 3 [2,2 dimethyl 3,4 dihydro (2h)benzopyran 6yl] 2e prop 2 enoate; n butyl 2,2 dimethylchroman 6 carboxamide; n butyl 3 [2,2 dimethyl 3,4 dihydro (2h)benzopyran 6yl] 2e prop 2 enoate; n butyl 5 hydroxy 2,2 dimethylchroman 7 carboxamide; n butyl 7 hydroxy 2,2 dimethylchroman 6 carboxamide; n hexyl 2,2 dimethylchroman 6 carboxamide; n hexyl 5 hydroxy 2,2 dimethylchroman 7 carboxamide; n hexyl 7 hydroxy 2,2 dimethylchroman 6 carboxamide; n n(2' ethylhexyl) 5 hydroxy 2,2 dimethylchroman 7 carboxamide; n pentyl 5 hydroxy 2,2 dimethylchroman 7 carboxamide; n propyl 3 [2,2 dimethyl 3,4 dihydro (2h)benzopyran 6yl] 2e prop 2 enoate; n(2' ethylhexyl) 2,2 dimethylchroman 6 carboxamide; n(2' ethylhexyl) 7 hydroxy 2,2 dimethylchroman 6 carboxamide; p nitrophenyl 3 [2,2 dimethyl 3,4 dihydro(2h)benzopyranp 6yl] 2e prop 2 enoate; p tetra butylphenyl 3 [2,2 dimethyl 3,4 dihydro(2h)benzopyran 6yl] 2e prop 2 enoate e -prop-2-enoate; phenyl 3 [2,2 dimethyl 3,4 dihydro (2h)benzopyran 6yl] 2e prop 2 enoate; tumor necrosis factor inhibitor; unclassified drug; unindexed drug; antiinflammatory activity; Article; drug design; drug potency; drug synthesis; endothelium cell; human; human cell; IC50; priority journal; protein expression; structure activity relation
Date of creation
02.11.2020
Date of change
02.11.2020
Short link
https://repository.rudn.ru/en/records/article/record/64467/
Share

Other records