biostudies-literatureUnknown8(51)De Tran QThe Zika virus (ZIKV) is believed to cause birth defects, and no anti-ZIKV drugs have been approved by medical organizations to date. Starting from antimicrobial lead compounds with a pyrazolo[3,4-d]pyridazine-7-one scaffold, we synthesized 16 derivatives and screened their ability to interfere with ZIKV infection utilizing a cell-based phenotypic assay. Of these, five compounds showed significant inhibition of ZIKV with a selective index value greater than 4.6. In particular, compound 9b showed the best anti-ZIKV activity with a selectivity index of 22.4 (half-maximal effective concentration = 25.6 μM and 50% cytotoxic concentration = 572.4 μM). Through the brine shrimp lethality bioassay, 9b, 10b, 12, 17a, and 19a showed median lethal doseACS omega48994-49008https://www.ebi.ac.uk/biostudies/studies/S-EPMC10753549biostudies-literatureZIKV Inhibitors Based on Pyrazolo[3,4-d]pyridazine-7-one Core: Rational Design, In Vitro Evaluation, and Theoretical Studies.PMC10753549Nguyen CQBich Hau VTMinh Nguyen THTuan NTQuan PMChau Thanh NQBinh TDNguyen HPMen TTCam TTDe Tran QDang QLThi Le MUTuan NDThu Thuy NTBuu Hue BTfalseZIKV Inhibitors Based on Pyrazolo[3,4-d]pyridazine-7-one Core: Rational Design, In Vitro Evaluation, and Theoretical Studies.The Zika virus (ZIKV) is believed to cause birth defects, and no anti-ZIKV drugs have been approved by medical organizations to date. Starting from antimicrobial lead compounds with a pyrazolo[3,4-d]pyridazine-7-one scaffold, we synthesized 16 derivatives and screened their ability to interfere with ZIKV infection utilizing a cell-based phenotypic assay. Of these, five compounds showed significant inhibition of ZIKV with a selective index value greater than 4.6. In particular, compound 9b showed the best anti-ZIKV activity with a selectivity index of 22.4 (half-maximal effective concentration = 25.6 μM and 50% cytotoxic concentration = 572.4 μM). Through the brine shrimp lethality bioassay, 9b, 10b, 12, 17a, and 19a showed median lethal dose2023-01-01T00:00:00Z2023 Dec2026-05-29T02:51:44.645Z2024-12-04T01:28:09.615ZS-EPMC107535493816275910.1021/acsomega.3c06612