TY - JOUR
T1 - Synthesis and cytotoxic activity of new 7-acetoxy-12-amino-14-deoxy andrographolide analogues
AU - Bunthawong, Rada
AU - Sirion, Uthaiwan
AU - Chairoungdua, Arthit
AU - Suksen, Kanoknetr
AU - Piyachaturawat, Pawinee
AU - Suksamrarn, Apichart
AU - Saeeng, Rungnapha
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Two new series of 19-silylether- and 19-formyl-7-acetyl-12-amino-14-deoxyandrographolide analogues were designed and synthesized from natural andrographolide via key step reactions including allylic hydroxylation, tandem CAE reaction and one pot formylation. Evaluation of their cytotoxicity against eight cancer cells line found 6e exhibited the highest activity on MCF-7 cancer cell (IC50 2.93) and comparable to the drug elipticin. Replacement of silylether at C-19 with formyl group exhibited selective activity on P-388 cell line. Computational studies revealed the amino group at C-12 and O-acetoxy at C-7 position play significant roles in cytotoxicity against MCF-7 cancer cells. Cytotoxicity of these two series highlights the importance of 12-substituted-14-deoxyandrographolide scaffold and these types of compounds could be employed in future developments against breast cancer.
AB - Two new series of 19-silylether- and 19-formyl-7-acetyl-12-amino-14-deoxyandrographolide analogues were designed and synthesized from natural andrographolide via key step reactions including allylic hydroxylation, tandem CAE reaction and one pot formylation. Evaluation of their cytotoxicity against eight cancer cells line found 6e exhibited the highest activity on MCF-7 cancer cell (IC50 2.93) and comparable to the drug elipticin. Replacement of silylether at C-19 with formyl group exhibited selective activity on P-388 cell line. Computational studies revealed the amino group at C-12 and O-acetoxy at C-7 position play significant roles in cytotoxicity against MCF-7 cancer cells. Cytotoxicity of these two series highlights the importance of 12-substituted-14-deoxyandrographolide scaffold and these types of compounds could be employed in future developments against breast cancer.
KW - 7-Acetoxy-12-amino-14-deoxyandrographolide derivatives
KW - Andrographis paniculata nees
KW - Andrographolide
KW - Cytotoxic activity
UR - http://www.scopus.com/inward/record.url?scp=85098674820&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2020.127741
DO - 10.1016/j.bmcl.2020.127741
M3 - Article
C2 - 33316411
AN - SCOPUS:85098674820
SN - 0960-894X
VL - 33
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
M1 - 127741
ER -
