title: Microwave assisted synthesis and QSAR study of novel NSAID acetaminophen conjugates with amino acid linkers.
abstract: Novel, non-steroidal anti-inflammatory drug (NSAID), acetaminophen conjugates 6a–l with amino acid linkers were synthesized utilizing benzotriazole chemistry. Biological data acquired for all the novel bis-conjugates showed (a) some bis-conjugates (6d, 6e, 6h, and 6k) exhibit more potent anti-inflammatory activity than their parent drugs, (b) the potent bis-conjugates show no visible stomach lesions in contrast to parent drugs which are highly ulcerogenic, and (c) that the potent bio-active compounds have no mortality rates or toxic symptoms at 5 fold the applied anti-inflammatory dosage. A statistically significant QSAR model describing the anti-inflammatory properties of 6a–l (N = 15, n = 3, R(2) = 0.891, R(2)cvOO = 0.770, R(2)cvMO = 0.796, F = 29.904, s(2) = 0.011) was obtained employing CODESSA-Pro that validated the observed bio-activity.
authors.affiliation: Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA. sspanda12@gmail.com charlesdennishall@gmail.com.
authors.forename: Anand D
authors.initials: AD
authors.lastname: Tiwari
authors.forename: Siva S
authors.initials: SS
authors.lastname: Panda
authors.forename: Adel S
authors.initials: AS
authors.lastname: Girgis
authors.forename: Sandhyamayee
authors.initials: S
authors.lastname: Sahu
authors.forename: Riham F
authors.initials: RF
authors.lastname: George
authors.forename: Aladdin M
authors.initials: AM
authors.lastname: Srour
authors.forename: Brian
authors.initials: B
authors.lastname: La Starza
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Asiri
authors.forename: C Dennis
authors.initials: CD
authors.lastname: Hall
authors.forename: Alan R
authors.initials: AR
authors.lastname: Katritzky
mesh_terms: D000082:Acetaminophen / Q000138:chemical synthesis / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry*; D008872:Microwaves; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen