title: Synthesis of a new 4-aza-2,3-didehydropodophyllotoxin analogues as potent cytotoxic and antimitotic agents.
abstract: A series of novel conjugates of 4-aza-2,3-didehydropodophyllotoxins (11a-w) were synthesized by a straightforward one-step multicomponent synthesis that demonstrated cytotoxicity against five human cancer cell lines (breast, oral, colon, lung and ovarian). All the twenty three compounds (11a-w) have been examined for the inhibition of tubulin polymerization. Among these compounds, 11a, 11k and 11p exhibited inhibition of polymerization tubulin comparable to podophyllotoxin apart from disruption of microtubule organization within the cells. Flow cytometric analysis showed that these compounds (11a, 11k and 11p) arrested the cell cycle in the G2/M phase of cell cycle leading to caspase-3 dependent apoptotic cell death.
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: Paidakula
authors.initials: P
authors.lastname: Suresh
authors.forename: Adla
authors.initials: A
authors.lastname: Mallareddy
authors.forename: Banala Ashwini
authors.initials: BA
authors.lastname: Kumar
authors.forename: Papagari Venkat
authors.initials: PV
authors.lastname: Reddy
authors.forename: Paidakula
authors.initials: P
authors.lastname: Raju
authors.forename: Jaki R
authors.initials: JR
authors.lastname: Tamboli
authors.forename: Thokhir B
authors.initials: TB
authors.lastname: Shaik
authors.forename: Nishant
authors.initials: N
authors.lastname: Jain
authors.forename: Shasi V
authors.initials: SV
authors.lastname: Kalivendi
mesh_terms: D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; 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; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism
chemical_list: C467920:4-aza-2,3-didehydropodophyllotoxin; D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D014404:Tubulin; D053148:Caspase 3; D011034:Podophyllotoxin