In vitro antitumor and antiviral activities of new benzothiazole and 1,3,4-oxadiazole-2-thione derivatives

• Published in: Acta pharmaceutica (Zagreb, Croatia) Croatia), 2008-06, Vol.58 (2), p.135-149
• Main Authors: Akhtar, Tashfeen, Hameed, Shahid, Al-Masoudi, Najim, Loddo, Roberta, Colla, Paolo
• Format: Article
• Language: English
• Subjects: 4-oksatiazoli; 4-oxathiazoles; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; antitumor activity; antitumorsko djelovanje; antiviral activity; Antiviral Agents - chemical synthesis; Antiviral Agents - pharmacology; antivirusno djelovanje; Benzothiazoles - chemical synthesis; Benzothiazoles - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Cytopathogenic Effect, Viral - drug effects; Dose-Response Relationship, Drug; Humans; Molecular Structure; Oxadiazoles - chemical synthesis; Oxadiazoles - pharmacology; Structure-Activity Relationship; substituted benzothiazoles; supstituirani benzotiazoli; Thiones - chemical synthesis; Thiones - pharmacology; Virus Replication - drug effects
• ISSN: 1330-0075; 1846-9558
• DOI: 10.2478/v10007-008-0007-2

A series of new benzothiazole derivatives 6a-h have been synthesized, in five steps, from substituted phenols via the 1,3,4-oxadiazole-2-thiones 5a-h. The in vitro antitumor activity of the compounds obtained was investigated and the benzothiazol derivatives 6d and 6e showed strong effects on leukaemia cell lines CCRF-CEM (CC50 = 12 ± 2 μmol L-1, 8 ± 1 μmol L-1, respectively). These compounds are leading candidates for further development. The title compounds were tested against representatives of several virus families containing single stranded RNA genomes, either positive-sense (ssRNA+), or negativesense (RNA-), and against double-stranded RNA genomes (dsRNA), as well as some Flaviviridae viruses. U pet reakcijskih koraka sintetizirana je serija novih derivata benzotiazola 6a-h polazeći iz supstituiranih fenola preko 1,3,4-oksadiazol-2-tiona 5a-h. Sintetizirani spojevi ispitani su na antitumorsko djelovanje. Benzotiazol derivati 6d i 6e pokazali su jak učinak na staničnu liniju leukemije CCRF-CEM (CC50 = 12 ± 2, odnosno 8 ± 1 μmol L-1). Ti su spojevi predvodni spojevi za daljnji razvoj. Nadalje, novi su spojevi testirani na djelovanje na nekoliko tipova virusa koji sadrže bilo pozitivni (ssRNA+) bilo negativni (RNA-) jednolančani RNA genom ili dvolančani RNA genom (dsRNA), te na neke Flaviviridae viruse.