title: Synthesis and Bioevaluation of Quaternary Centered 3-hydroxy-3 (alkynyl)indolin-2-one Derivatives as Potential Cytotoxic Agents and Akt Kinase Inhibitors.
abstract: Alkynes are fundamental building blocks in synthetic chemistry with high pharmaceutical applications. Among the bioactive acetylenic molecules, propargylic alcohol is most important as almost all the marketed drugs contains quaternary centered propargylic alcohol functionality.
  
  
  
  In this study we have synthesised and evaluated 3-hydroxy-3-ethynylindolin-2-one derivatives for in vitro cytotoxic activity.
  
  
  
  An expeditious method for direct alkynylation of isatins (ketones) has been developed using tetrabutylammonium fluoride (TBAF) as a catalyst in THF solvent at room temperature under metal-free conditions. Furthermore, this method is an economically viable process that also compliments green aspects like being a ligand/metal free process under ambient conditions. This reaction tolerated a wide range of substrates with good to excellent yields (80-94%).
  
  
  
  The results showed that the synthesized compounds (4m, 4n and 4p) has the ability to inhibit Akt kinase activity with IC50 values ranging from 7.7 to 9.8 µM.
  
  
  
  All the 3-hydroxy-3-ethynylindolin-2-one derivatives were subjected for in vitro cytotoxic activity on five different cancer cell lines. Further, the synthesized compounds (4m, 4n and 4p) were evaluated for their ability to inhibit Akt kinase activity and exhibited good inhibition with IC50 values ranging from 7.7 to 9.8 µM..
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607, India.
authors.forename: P Sai
authors.initials: PS
authors.lastname: Prathima
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607, India.
authors.forename: R
authors.initials: R
authors.lastname: Bikshapathi
authors.affiliation: Medicinal Chemistry and Pharmacology Division, (IICT), Hyderabad, India.
authors.forename: Y
authors.initials: Y
authors.lastname: Poornachandra
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607, India.
authors.forename: V
authors.initials: V
authors.lastname: Himabindu
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607, India.
authors.forename: G Jagadeesh
authors.initials: GJ
authors.lastname: Kumar
authors.affiliation: X-ray Crystallography Division(IICT), Hyderabad, India.
authors.forename: N
authors.initials: N
authors.lastname: Jagadeesh
authors.affiliation: Medicinal Chemistry and Pharmacology Division, (IICT), Hyderabad, India.
authors.forename: C Ganesh
authors.initials: CG
authors.lastname: Kumar
authors.affiliation: Crop Protection Chemicals Division, CSIR-Indian Institute of Chemical Technology (IICT), Uppal Road, Tarnaka, Hyderabad, 500 607, India.
authors.forename: V Jayathirtha
authors.initials: VJ
authors.lastname: Rao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D007211:Indoles; D047428:Protein Kinase Inhibitors; C456900:indolin-2-one; D051057:Proto-Oncogene Proteins c-akt
keywords: 3-hydroxy-3-ethynylindolin-2-one derivatives.; Akt kinase activity; Alkynylation; N-substituted isatins; TBAF; oxindoles