title: Evaluation of cytotoxic potential of newly synthesized antiviral aminopyrazoloquinoline derivatives.
abstract: In the present study, we screened newly synthesized antiviral aminopyrazoloquinoline derivatives for cytotoxic potential in human normal and breast cancer cell lines using apoptosis as biomarker. These derivatives and the well known antiviral drug, acyclovir, were incubated with the normal (MCF-10A, MCF-12A) and cancer (MCF-7, MDA-MB-231) cell lines at 10, 50 and 100 μM for 72 h at 37°C. Both the parent compounds and their sugar derivatives were found to be differentially cytotoxic in various cell lines. MCF-7 cells were more or less completely resistant to all these compounds while MDA-MB-231 cells were significantly killed by apoptosis. The methoxy derivative of aminopyrazoloquinoline (compound 3) was found to be the most cytotoxic in the normal breast epithelial cell lines (MCF-10A and MCF-12A) and MDA-MB-231 cell lines at 100 μM killing over 90% of the cells with up to 80% apoptosis. Interestingly MCF-7 cells showed only up to 50% killing at 100 μM dose with less than 20% apoptosis. Acyclovir did not cause any cytotoxicity, apoptosis or cell cycle arrest in any of the cells lines at the doses tested. Our results suggest that the newly synthesized antiviral compounds have an associated risk of being cytotoxic compared to the acyclovir.
authors.affiliation: Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia;
authors.forename: Jamal M
authors.initials: JM
authors.lastname: Arif
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kunhi
authors.forename: Manogaran P
authors.initials: MP
authors.lastname: Subramanian
authors.forename: Adnan A
authors.initials: AA
authors.lastname: Bekhit
authors.forename: Ola A
authors.initials: OA
authors.lastname: El-Sayed
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Hussein
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Aboul-Enein
authors.forename: Fahad M
authors.initials: FM
authors.lastname: Al-Khodairy
keywords: DNA damage; MCF-10A; MCF-12; MCF-7; MDA-MB-231; aminopyrazoloquinoline; apoptosis