Isolation of new monoterpene coumarins from Micromelum minutum leaves and their cytotoxic activity against Leishmania major and cancer cells

On the basis of a leishmanicidal assay-guided isolation, two new monoterpene coumarins, minutin A and minutin B, were purified from Micromelum minutum leaves together with four known coumarins, 8,4″-dihydroxy-3″,4″-dihydrocapnolactone-2′,3′-diol, 8-hydroxyisocapnolactone-2′,3′-diol, 8-hydroxy-3″,4″-dihydrocapnolactone-2′,3′-diol, and clauslactone E. Among these compounds, minutin A, minutin B, 8-hydroxyisocapnolactone-2′,3′-diol and clauslactone E showed a significant cytotoxic activity against Leishmania major with IC50 values of 26.2, 20.2, 12.1, and 9.8 μM, respectively, while 8,4″-dihydroxy-3″4″-dihydrocapnolactone-2′,3′-diol and 8-hydroxy-3″,4″-dihydrocapnolactone-2′,3′-diol were not active. However, all these compounds exhibited some inhibitory activity against one or more lung adenocarcinoma (SBC3 and A549) and leukaemia (K562, and K562/ADM) cell lines. Amongst these, clauslactone E, minutin B and 8-hydroxyisocapnolactone-2′,3′-diol possessed the strongest cytotoxic activity against SBC3, A549, K562, and K562/ADM cell lines, with IC50 values of 3.7, 10.4, 12.1, and 10.8 μM for clauslactone E; 9.6, 17.5, 8.7 and 6.7 μM for minutin B; 8.8, 10.1, 16.9, and 10.1 μM for 8-hydroxyisocapnolactone-2′,3′-diol, respectively.