title: Novel hybrid nocodazole analogues as tubulin polymerization inhibitors and their antiproliferative activity.
abstract: We describe the design, synthesis and SAR profiling of a series of novel combretastatin-nocodazole conjugates as potential anticancer agents. The thiophene ring in the nocodazole moiety was replaced by a substituted phenyl ring from the combretastatin moiety to design novel hybrid analogues. The hydroxyl group at the ortho position in compounds 2, 3 and 4 was used as the conformationally locking tool by anticipated six-membered hydrogen bonding. The bioactivity profiles of all compounds as tubulin polymerization inhibitors and as antiproliferative agents against the A-549 human lung cancer cell line were investigated Compounds 1 and 4 showed μM IC50 values in both assays.
authors: Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India.
authors: Sangram S
authors: SS
authors: Kale
authors: Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India.
authors: Ganesh S
authors: GS
authors: Jedhe
authors: National Centre for Cell Science, University of Pune Campus, Ganeshkhind, Pune 411 007, Maharashtra, India.
authors: Sachin N
authors: SN
authors: Meshram
authors: National Centre for Cell Science, University of Pune Campus, Ganeshkhind, Pune 411 007, Maharashtra, India.
authors: Manas K
authors: MK
authors: Santra
authors: Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, United States.
authors: Ernest
authors: E
authors: Hamel
authors: Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India. Electronic address: gj.sanjayan@ncl.res.in.
authors: Gangadhar J
authors: GJ
authors: Sanjayan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D015739:Nocodazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D058105:Polymerization / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D014404:Tubulin; D015739:Nocodazole
keywords: Anticancer; Colchicine; Nocodazole; Tubulin binding