{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin ACK"],"funding":["The Second Century Fund (C2F), Chulalongkorn University","Thailand Science Research and Innovation Fund"],"pagination":["20858"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9718795"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(1)"],"pubmed_abstract":["Caffeic acid derivatives containing amide moieties similar to those of finasteride and dutasteride were synthesized. An in vitro inhibitory activity evaluation of caffeic acid (1) and its amide derivatives (2 - 4) against the steroid 5α-reductase type 1 (SRD5A1) produced by human keratinocyte cells coupled with the non-radioactive high-performance thin-layer chromatography detection revealed that caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide (4) was a promising non-steroidal suppressor, with a half-maximal inhibitory concentration (IC<sub>50</sub>) of 1.44 ± 0.13 µM and relatively low cytotoxicity with an IC<sub>50</sub> of 29.99 ± 8.69 µM. The regulatory role of compound 4 against SRD5A1 involved both suppression of SRD5A1 expression and mixed mode SRD5A1 inhibition. The K<sub>i</sub> value of compound 4 was 2.382 µM based on the whole-cell kinetic studies under specific conditions. Molecular docking and molecular dynamics simulations with AlphaFold generated the human SRD5A1 structure and confirmed the stability of compound 4 at the SRD5A1 catalytic site with greater interactions, including hydrogen bonding of the key M119 amino-acid residue than those of finasteride and dutasteride. Thus, compound 4 shows the potential for further development as an SRD5A1 suppressor for androgenic alopecia treatment."],"journal":["Scientific reports"],"pubmed_title":["Caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide as a non-steroidal inhibitor for steroid 5α-reductase type 1 using a human keratinocyte cell-based assay and molecular dynamics."],"pmcid":["PMC9718795"],"funding_grant_id":["CU_FRB640001_23_33_8"],"pubmed_authors":["Netcharoensirisuk P","Chansriniyom C","Chaotham C","De-Eknamkul W","Sukma W","Rungrotmongkol T","Sanachai K","Lin ACK","Chamni S"],"additional_accession":[]},"is_claimable":false,"name":"Caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide as a non-steroidal inhibitor for steroid 5α-reductase type 1 using a human keratinocyte cell-based assay and molecular dynamics.","description":"Caffeic acid derivatives containing amide moieties similar to those of finasteride and dutasteride were synthesized. An in vitro inhibitory activity evaluation of caffeic acid (1) and its amide derivatives (2 - 4) against the steroid 5α-reductase type 1 (SRD5A1) produced by human keratinocyte cells coupled with the non-radioactive high-performance thin-layer chromatography detection revealed that caffeic acid N-[3,5-bis(trifluoromethyl)phenyl] amide (4) was a promising non-steroidal suppressor, with a half-maximal inhibitory concentration (IC<sub>50</sub>) of 1.44 ± 0.13 µM and relatively low cytotoxicity with an IC<sub>50</sub> of 29.99 ± 8.69 µM. The regulatory role of compound 4 against SRD5A1 involved both suppression of SRD5A1 expression and mixed mode SRD5A1 inhibition. The K<sub>i</sub> value of compound 4 was 2.382 µM based on the whole-cell kinetic studies under specific conditions. Molecular docking and molecular dynamics simulations with AlphaFold generated the human SRD5A1 structure and confirmed the stability of compound 4 at the SRD5A1 catalytic site with greater interactions, including hydrogen bonding of the key M119 amino-acid residue than those of finasteride and dutasteride. Thus, compound 4 shows the potential for further development as an SRD5A1 suppressor for androgenic alopecia treatment.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-05-28T01:10:58.977Z","creation":"2025-04-19T22:48:54.302Z"},"accession":"S-EPMC9718795","cross_references":{"pubmed":["36460729"],"doi":["10.1038/s41598-022-25335-7"]}}