Naslov
Antimycobacterial screening of four series of primaquine derivatives

Autori
Jampilek, Josef ; Pospišilova, Sarka ; Michnova , Hana ; Pavić, Kristina ; Perković, Ivana ; Zorc, Branka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts / Basarić , Nikola ; Namjesnik, Danijel ; Perković, Ivana ; Stepanić, Višnja - Zagreb : Hrvatsko kemijsko društvo, 2017, 244-244

ISBN
978-953-55232-8-4

Skup
10th Joint Meeting on Medicinal Chemistry

Mjesto i datum
Srebreno, Hrvatska; Dubrovnik, Hrvatska, 25.06.2017. - 28.06.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
primaquine ; urea ; bis-urea ; acylsemicarbazide ; amide ; antimycobacterial activity

Sažetak
Primaquine (PQ) is a well known antimalarial drug active against all species of parasite causing human malaria, including multi- resistant P. falciparum strains. Primaquine has been also identified as orally administrated drug capable of inhibiting M. tuberculosis growth.[1] In several papers, we have described preparation of almost hundred various PQ derivatives and their evaluation as potential antiproliferative, antioxidative, antimalarial, antimicrobial and antiviral agents.[2-7] Here we report the results of antimycobacterial screening of four groups of PQ derivatives: amides 1a-k, ureas 2a-s, semicarbazides 3a-c and bis-ureas 4a-u. Antimycobacterial evaluation was performed in vitro against three different Mycobacterium species: M. tuberculosis H37Ra ATCC 25177 (MTB), well characterised clinical isolates of M. avium complex CIT19/06 (MAC), and M. avium subsp. paratuberculosis CIT03 (MAP). The results were compared with PQ diphosphate and the standard antitubercular drugs isoniazid (INH), rifampicin (RIF) and ciprofloxacin (CPX). Most of the compounds of series 1 and 2 showed high activity against MAP, comparable or even higher than the relevant drug CPX, and weak or no activity against the other two bacteria. Cinnamic acid amide 1a and bis-CF3 cinnamic acid amide 1k were active against all three Mycobacterium species comparable or slightly higher than the reference drugs. PQ urea derivatives 2f-p with hydroxyl, halogen and particularly trifluoromethyl substituted benzene ring exerted very strong antimycobacterial activity towards all three tested bacteria, stronger than PQ and the reference drugs. In general, meta substituted derivatives were more active than analogues para derivatives. The benzene substituted ureas were also more active than urea derivatives with cycloalkyl or hydroxyalkyl moieties. Semicarbazide 3a showed similar activity as PQ, while the other two semicarbazides were inactive. In general, bis-urea derivatives were less active than the analogues urea derivatives sharing the same scaffold, differing only in the spacer type. Out of 21 evaluated bisurea derivatives only p-Cl, m-CF3 phenyl derivative 4p, benzhydryl derivatives 4t and 4u and bis-PQ derivative 4s showed high activity, higher than the all three reference drugs.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Farmacija

POVEZANOST RADA