title: Semisynthesis, ex vivo evaluation, and SAR studies of coumarin derivatives as potential antiasthmatic drugs.
abstract: Asthma is a chronic inflammatory disorder that causes contraction in the smooth muscle of the airway and blocking of airflow. Reversal the contractile process is a strategy for the search of new drugs that could be used for the treatment of asthma. This work reports the semisynthesis, ex vivo relaxing evaluation and SAR studies of a series of 18 coumarins. The results pointed that the ether derivatives 1-3, 7-9 and 13-15 showed the best activity (Emax = 100%), where compound 2 (42 μM) was the most potent, being 4-times more active than theophylline (positive control). The ether homologation (methyl, ethyl and propyl) in position 7 or positions 6 and 7 of coumarins lead to relaxing effect, meanwhile formation of esters generated less active compounds than ethers. The SAR analysis showed that it is necessary the presence of two small ether groups and the methyl group at position 4 (site 3) encourage biological activity through soft hydrophobic changes in the molecule, without drastically affecting the cLogP.
authors.affiliation: Laboratorio de Farmacognosia y Química de Productos Naturales, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Col. Chamilpa, 62209 Cuernavaca, Morelos, Mexico.
authors.forename: Amanda
authors.initials: A
authors.lastname: Sánchez-Recillas
authors.affiliation: Laboratorio de Química Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Col. Chamilpa, 62209 Cuernavaca, Morelos, Mexico. Electronic address: gabriel_navarrete@uaem.mx.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vázquez
authors.affiliation: Laboratorio de Química Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Col. Chamilpa, 62209 Cuernavaca, Morelos, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Hidalgo-Figueroa
authors.affiliation: Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Col. Chamilpa, 62209 Cuernavaca, Morelos, Mexico.
authors.forename: María Yolanda
authors.initials: MY
authors.lastname: Rios
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, 54090 Tlalnepantla, Estado de México, Mexico.
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Ibarra-Barajas
authors.affiliation: Laboratorio de Farmacognosia y Química de Productos Naturales, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Avenida Universidad 1001, Col. Chamilpa, 62209 Cuernavaca, Morelos, Mexico. Electronic address: enoch@uaem.mx.
authors.forename: Samuel
authors.initials: S
authors.lastname: Estrada-Soto
mesh_terms: D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects*
chemical_list: D018927:Anti-Asthmatic Agents; D003374:Coumarins; C030123:coumarin
keywords: Asthma; Coumarins; Natural products; Pharmacophoric group; SAR; Tracheal rings