Flavonoids are natural products widely recognized for their plurality of applications such as antiviral, antiproliferative, antitumor activities and, antioxidant properties . The flavanone naringenin is presented in citrus fruits and has been studied to combat recurrent diseases that still lack effective treatment . Research groups have been investing efforts to the development of new, safe and active candidates to combat these agents or conditions and despite good results recently reported against the Zika virus (ZIKV) and tumor cells, the use of citrus naringenin is limited due to its low bioavailability . Structural exchanges through functionalization, for example, attaching lipophilic groups instead of hydroxyl groups, can further enhance biological properties . Here, the synthesis and characterization of regioselective naringenin mono-7-O-ethers and both mono and di-fatty acid esters, structurally lipophilic ones were demonstrated . Finally, in vitro studies of anti-ZIKV action and antiproliferative activities against melanoma (B16-F10) and breast carcinoma (4T1) cells showed the ether derivatives were actives, with IC ranging from 6.76 , 18.5 and 22.6 μM to 28.53 , 45.1 and 32.3 μM referring to ZIKV, B16-F10 and 4T1 cell lines, respectively . The lipophilic ethers present the ability to inhibit selectively ZIKV-replication in human cells and inhibitions . This class of modifications in flavonoid molecules could be further explore in the future development of specific anti-ZIKV compounds.