title: Synthesis and biological evaluation of 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates.
abstract: A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport.
authors.affiliation: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého 1/3, 612 42 Brno, Czech Republic ; Medis International a.s., Průmyslová 16, 747 23 Bolatice, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Tengler
authors.forename: Iva
authors.initials: I
authors.lastname: Kapustíková
authors.forename: Matúš
authors.initials: M
authors.lastname: Peško
authors.forename: Rodney
authors.initials: R
authors.lastname: Govender
authors.forename: Stanislava
authors.initials: S
authors.lastname: Keltošová
authors.forename: Petr
authors.initials: P
authors.lastname: Mokrý
authors.forename: Peter
authors.initials: P
authors.lastname: Kollár
authors.forename: Jim
authors.initials: J
authors.lastname: O'Mahony
authors.forename: Aidan
authors.initials: A
authors.lastname: Coffey
authors.forename: Katarína
authors.initials: K
authors.lastname: Král'ová
authors.forename: Josef
authors.initials: J
authors.lastname: Jampílek
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001565:Benzoates / Q000138:chemical synthesis* / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000494:pharmacology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000187:drug effects*; D018724:Spinacia oleracea / Q000187:drug effects; D014475:Uncoupling Agents / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001565:Benzoates; D002219:Carbamates; D014475:Uncoupling Agents