Synthesis of novel anticancer iridoid derivatives and their cell cycle arrest and caspase dependent apoptosis.
Nyctanthes arbortristis Linn (Oleaceae) is widely distributed in sub-Himalayan regions and southwards to Godavari, India commonly known as Harsingar and Night Jasmine. In continuation of our drug discovery programme on Indian medicinal plants, we isolated arbortristoside-A (1) and 7-O-trans-cinnamoyl 6β-hydroxyloganin (2) from the seeds of N. Arbortristis, which exhibited moderate in vitro anticancer activity. Chemical transformation of 2 led to significant improvement in the activity in derivative 8 and 15 against HepG2 (human hepatocellular carcinoma), MCF-7 (breast adenocarcinoma) cell lines. The compounds 8 and 15 were also capable of cell cycle arrest and caspase dependent apoptosis in HepG2 cell lines. These iridoid derivatives hold promise for developing safer alternatives to the marketed drugs.
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 001, UP, India.
Sukanya
S
Pandeti
Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226 001, UP, India.
Komal
K
Sharma
Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226 001, UP, India. Electronic address: bsreddy@cdri.res.in.
Surendar Reddy
SR
Bathula
Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 001, UP, India. Electronic address: t_narendra@cdri.res.in.
Narender
N
Tadigoppula
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002934:Cinnamates / Q000494:pharmacology / Q000627:therapeutic use*; D056945:Hep G2 Cells; D006801:Humans; D007194:India; D057888:Iridoid Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D039823:Iridoids / Q000494:pharmacology / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D029592:Oleaceae / Q000737:chemistry*; D008517:Phytotherapy; D010936:Plant Extracts / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D012639:Seeds
C586936:7-O-trans-cinnamoyl-6beta-hydroxyloganin; D000972:Antineoplastic Agents, Phytogenic; D002934:Cinnamates; D057888:Iridoid Glucosides; D039823:Iridoids; D010936:Plant Extracts; C528442:arbortristoside A; D020169:Caspases
7-O-trans-cinnamoyl 6β-hydroxyloganin derivatives; Anticancer agents; Apoptosis; Arbortristoside-A; Nyctanthes arbortristis