title: Investigation of podophyllotoxin esters as potential anticancer agents: synthesis, biological studies and tubulin inhibition properties.
abstract: A series of fifteen podophyllotoxin derived esters have been synthesized and their anti-cancer properties have been evaluated against A549 (lung cancer), DU-145 (prostate cancer), HepG2 (liver cancer), HeLa (cervical cancer) and MCF-7 (breast cancer) cell lines. Five compounds of the series 8a, 8g-h, 8m and 8o showed IC50 values in the range of 0.71-10.94 μM. Among compounds, 8g and 8h showed significant cytotoxicity towards all the types of cancer studied. Cell cycle analysis revealed that the compounds 8a, 8m and 8o inhibit proliferation by cell cycle arrest. Also Hoechst-positive nucleus indicating apoptosis of these cells was observed in presence of 8g-h. Further studies revealed that these compounds inhibit tubulin polymerization and leads to the inactivation of AKT/PKB that are known to play an important role in the proliferation of cancer cells.
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad 500 007, India.
authors.forename: Mohd Adil
authors.initials: MA
authors.lastname: Shareef
authors.affiliation: Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad 500 007, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Duscharla
authors.affiliation: Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad 500 007, India.
authors.forename: G
authors.initials: G
authors.lastname: Ramasatyaveni
authors.affiliation: Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad 500 007, India.
authors.forename: Neha R
authors.initials: NR
authors.lastname: Dhoke
authors.affiliation: Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad 500 007, India.
authors.forename: Amitava
authors.initials: A
authors.lastname: Das
authors.affiliation: Center for Chemical Biology, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad 500 007, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ummanni
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Hyderabad 500 007, India. Electronic address: aksrivastava@iict.res.in.
authors.forename: Ajay Kumar
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D014404:Tubulin; D050257:Tubulin Modulators; D011034:Podophyllotoxin
keywords: Anticancer agents; CA-4; Podophyllotoxin; Tubulin polymerization inhibition