title: Synthesis and anticancer activity of 4β-alkylamidochalcone and 4β-cinnamido linked podophyllotoxins as apoptotic inducing agents.
abstract: A series of 4β-alkylamidochalcone and 4β-cinnamido linked podophyllotoxin congeners have been synthesized. All the twenty nine compounds were evaluated for anticancer activity against five human cancer cell lines (A-549, A375, MCF-7, HT-29 and ACHN). Some of the synthesized compounds showed good anticancer activity that is comparable to etoposide. The IC(50) of compounds 17a and 17f is 2.7 and 2.1 μM respectively against A-549 cancer cell line. Flow cytometric analysis showed that these two compounds arrested the cell cycle in the G2/M phase leading to caspase-3 dependent apoptotic cell death. Further, Hoechst 33258 staining and DNA fragmentation assay also suggested that 17a and 17f induced cell death by apoptosis.
authors.affiliation: Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India. ahmedkamal@iict.res.in
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.forename: Adla
authors.initials: A
authors.lastname: Mallareddy
authors.forename: Paidakula
authors.initials: P
authors.lastname: Suresh
authors.forename: V
authors.initials: V
authors.lastname: Lakshma Nayak
authors.forename: Rajesh V C R N C
authors.initials: RV
authors.lastname: Shetti
authors.forename: N
authors.initials: N
authors.lastname: Sankara Rao
authors.forename: Jaki R
authors.initials: JR
authors.lastname: Tamboli
authors.forename: Thokhir B
authors.initials: TB
authors.lastname: Shaik
authors.forename: M V P S
authors.initials: MV
authors.lastname: Vishnuvardhan
authors.forename: S
authors.initials: S
authors.lastname: Ramakrishna
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002599:Chalcone / Q000737:chemistry*; D002934:Cinnamates / Q000737:chemistry*; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D011034:Podophyllotoxin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002934:Cinnamates; C029010:cinnamic acid; D002599:Chalcone; D053148:Caspase 3; D011034:Podophyllotoxin