title: An Integrated Multi-QSAR Modeling Approach for Designing Knoevenagel- Type Indoles with Enhancing Cytotoxic Profiles.
abstract: BACKGROUND
  Unconventional Knoevenagel-type indoles have been the topic of interest of many synthetic chemists because of its promising efficacy in different diseases including cancer.
  
  
  OBJECTIVE
  To explore the structural requirements of Knoevenagel-type cytotoxic indoles for higher efficacy.
  
  
  METHODS
  Multi-QSAR modeling (MLR, ANN, SVM, Bayesian classification, HQSAR and Topomer CoMFA) was performed on these analogs.
  
  
  RESULTS
  All these modeling techniques were validated individually and interpreted with the experimental SAR observations. Phenyl or p-methoxyphenyl substitution at 2nd position, electron withdrawing groups (such as sulphonyl, cyano etc.) at 3rd position and methoxy substation at 5th position of the indole scaffold may favor cytotoxicity. Eight new indole molecules were predicted from the developed QSAR models.
  
  
  CONCLUSIONS
  These newly designed compounds may bind to the colchicine binding site of the tubulin protein as suggested by the molecular docking study.
authors.affiliation: Laboratory of Drug Design and Discovery, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar 470003, (MP), India.|Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P.O. Box 17020, Jadavpur University, Kolkata 700032, (WB), India.
authors.forename: Sk Abdul
authors.initials: SA
authors.lastname: Amin
authors.affiliation: Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P.O. Box 17020, Jadavpur University, Kolkata 700032, (WB), India.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Adhikari
authors.affiliation: Natural Science Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P.O. Box 17020, Jadavpur University, Kolkata 700032, (WB), India.
authors.forename: Tarun
authors.initials: T
authors.lastname: Jha
authors.affiliation: Laboratory of Drug Design and Discovery, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar 470003, (MP), India.
authors.forename: Shovanlal
authors.initials: S
authors.lastname: Gayen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001499:Bayes Theorem; D003198:Computer Simulation; D017076:Computer-Aided Design; D003603:Cytotoxins / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D008954:Models, Biological; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D007211:Indoles
keywords: ANN; Bayesian classification model; HQSAR; Knoevenagel-type indoles; SVM; Topomer
  CoMFA; cytotoxic agents; molecular docking.