JOURNAL ARTICLE

Design, synthesis, and biologic evaluation of novel chrysin derivatives as cytotoxic agents and caspase-3/7 activators

Buthina Abdallah Al-Oudat, Mohammad Ali Alqudah, Suaad Abdallah Audat, Qosay Ali Al-Balas, Tamam El-Elimat, Mohammad Abdelhafeez Hassan, Islam Nawaf Frhat, Marwah Mohammad Azaizeh
Drug Design, Development and Therapy 2019, 13: 423-433
30774307

Background: Chrysin (5,7-dihydroxyflavone) is a widely distributed natural flavonoid found in many plant extracts, honey and propolis. Several studies revealed that chrysin possesses multiple biological activities including anti-cancer effects. It has been established that activation of apoptosis is the key molecular mechanism responsible for the cytotoxic potential of chrysin. The objective of this study was to design and synthesize potent chrysin analogues as potential cytotoxic agents.

Methods: A series of chrysin derivatives ( 3a-m ) bearing N'-alkylidene/arylideneacetohydrazide moiety were designed, synthesized, and evaluated for their antiproliferative activity against two human breast cancer cell lines, MDA-MB-231 and MCF-7 by applying the MTT colorimetric assay. Selected compounds were tested for their ability to induce apoptosis through caspase 3/7 activation in MDA-MB-231 cells only since MCF-7 cells lack procaspase 3.

Results: Compounds ( 3a-m ) were obtained as geometrical isomers ( E/Z isomers) in good yields upon treatment of hydrazide 5 with different aliphatic and aromatic aldehydes. Most of the synthesized compounds demonstrated moderate-to-good activity against both cell lines. The cytotoxicity results revealed the importance of lipophilic moieties at C-4 position of ring D in imparting the cytotoxic activities to the compounds. Compound 3e with 4-benzyloxy substituent was found to be the most active among the synthesized compounds with IC50 3.3 µM against MDA-MB-231 and 4.2 µM against MCF-7 cell lines. The cytotoxic potential of compound 3e is comparable to that of the well-known anti-cancer agent doxorubicin. In addition, compounds substituted with fluoro ( 3b ), nitro ( 3h ), and dimethylamino ( 3j ) exhibited good cytotoxicity with IC50 <6.5 µM against MDA-MB-231 and <12 µM against MCF-7. Selected compounds were able to induce apoptosis in MDA-MB-231 cells as indicated by caspase-3 and/or -7 activation.

Conclusion: Our results show that the newly designed chrysin derivatives exert anticancer activity in human breast cancer cell lines, MDA-MB-231 and MCF-7. Therefore, they can be considered as leads for further development of more potent and selective cytotoxic agents.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
30774307
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"