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The present study was investigated the cytotoxic ac tivity of a new aaptaminoid of A. aaptos against hu man myeloid leukemia cell line HL-60 and murine myelomonocytic leukemia cell line WEHI-3B, as well as the mode of cells death and antiviral activity against Herpes simplex virus type 1 HSV-1, infected normal mammalian cell s, Cercopithecus aethiops African green monkey kidney cell line VERO. Cell viability was evaluated by Met hyl Thiazole Tetrazolium (MTT) assay, following the ind uction of apoptosis assessment by light microscopy and fluorescence microscopy (Acridine orange/ Propidium iodide (AO/PI) double staining analysis) while usi ng hydrogen peroxide (H 2 O 2 ) as a standard. The anti-HSV-1 activity was evalua ted using neutral red uptake assay. A new alkaloid 3-(phenethylamino)demethyl(oxy)aapta mine(8-methoxy-2-(phenethylamino)-9H-benzo[d,e][1,6 ] naphthyridin-9-one) ( 1 ) and aaptamine (8,9-dimethoxy-1H-benzo[d,e][1,6]-n aphthyridin) ( 2 ) strongly reduced HL- 60 viability while also showing cytotoxicity agains t WEHI-3B, in which the mode of both cells death wa s through induction of apoptosis. In anti-herpetic investigat ion against HSV-1, only compound 2 showed strong anti-HSV-1 activity. The compounds however did not exert signi ficant cytotoxic effect on VERO, confirming their t umour- selective cytotoxicity. Result concluded that compounds 1 and 2 produced a good cytotoxicity activity on HL-60 and WEHI-3B. Both compounds inhibited the cells via ap optotic cell death mechanism. In addition, compound 2 also exhibited a good antivirus activity on HSV-1.
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Author(s): M R Zalilawati Yosie Andriani Khozirah Shaari Nathalie Bourgougnon Abd Manaf Ali Tengku Sifzizul Tengku Muhammad and Habsah Mohamad
Aaptos aaptos, aaptaminoids, cytotoxicity, apoptosis, HSV-1, AO/PI, apoptosis, anti HSV-1 activity, 3-(phenethylamino) demethyl(oxy)aaptamine