title: Synthesis of chalcone-amidobenzothiazole conjugates as antimitotic and apoptotic inducing agents.
abstract: A series of chalcone-amidobenzothiazole conjugates (9a-k and 10a,b) have been synthesized and evaluated for their anticancer activity. All these compounds exhibited potent activity and the IC(50) of two potential compounds (9a and 9f) against different cancer cell lines are in the range of 0.85-3.3 μM. Flow cytometric analysis revealed that these compounds induced cell cycle arrest at G2/M phase in A549 cell line leading to caspase-3 dependent apoptotic cell death. The tubulin polymerization assay (IC(50) of 9a is 3.5 μM and 9f is 5.2 μM) and immuofluorescence analysis showed that these compounds effectively inhibit microtubule assembly at both molecular and cellular levels in A549 cells. Further, Annexin staining also suggested that these compounds induced cell death by apoptosis. Moreover, docking experiments have shown that they interact and bind efficiently with tubulin protein. Overall, the current study demonstrates that the synthesis of chalcone-amidobenzothiazole conjugates as promising anticancer agents with potent G2/M arrest and apoptotic-inducing activities via targeting tubulin.
authors.affiliation: Division of Organic Chemistry, CSIR-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: Thokhir B
authors.initials: TB
authors.lastname: Shaik
authors.forename: V
authors.initials: V
authors.lastname: Lakshma Nayak
authors.forename: Chandan
authors.initials: C
authors.lastname: Kishor
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: S
authors.initials: S
authors.lastname: Ramakrishna
authors.forename: Anthony
authors.initials: A
authors.lastname: Addlagatta
mesh_terms: D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D052160:Benzothiazoles / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002599:Chalcone / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D020128:Inhibitory Concentration 50; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism
chemical_list: D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D014404:Tubulin; D002599:Chalcone; D053148:Caspase 3; C005465:benzothiazole