There is an urgent need for the design and development of new and safer drugs for the treatment of
HIV infection, active against the currently resistant viral strains. New derivatives of the non-steroidal
anti-inflammatory drug indomethacin bearing benzimidazoles, benzothiazole, purine and pyridine
residues 8 – 13 were synthesized with the aim of developing new non-nucleoside reverse transcriptase
inhibitors (NNRTIs). Alternatively, new imine analogs 16 – 20 were synthesized from condensation of
indomethacinyl hydrazide 15, prepared from the ester 14, with various ketone precursors. Treatment
of 15 with phenyl isothiocyanate or triethyl orthoformate afforded the phenylcarbonothioyl and the
oxadiazole derivatives 21 and 22, respectively. The new compounds were assayed against HIV-1 and
HIV-2 in MT-4 cells. Compounds 9 and 10 were the most active in inhibiting HIV-2 and HIV-1,
respectively, with EC50 ≥ 17.60 µ g mL− 1 and > 1.15 µ g mL− 1 (therapeutic indexes (SI) of ≥ 3
and < 1, respectively), and are leading candidates for further development.
أ. د ناظر نجم عبدالله الكطراني | Nadhir Najim Abdullah Jafar | 4595