title: Docking and QSAR Studies of 1,4-Dihydropyridine Derivatives as Anti- Cancer Agent.
abstract: BACKGROUND
  The multidrug resistance (MDR) of cancer cells has become a great barrier to the success of chemotherapy.
  
  
  OBJECTIVE
  In this study, quantitative structure activity relationship (QSAR) modeling was applied to 46 1,4-dihydropyridine structures (DHPs), and some selected compounds were docked.
  
  
  METHODS
  QSAR was used to generate models and predict the MDR inhibitory activity for a series of 1,4-dihydropyridines (DHP). The DHPs were built and optimized using the Sybyl program (x1.2 version). Descriptor generation was done by DRAGON package. Docking was carried out using Auto Dock 4.2 software. Multiple linear regression, and partial least square were performed as QSAR modelgeneration methods. External validation, cross-validation (leave one out) and y-randomization were used as validation methods.
  
  
  RESULTS
  The constructed model using stepwise-MLR and GA-PLS revealed good statistical parameters. In the final step all compounds were divided into two parts: symmetric (PLS) and asymmetric (MLR) 1,4-dihydropyridines and two other models were built. The square correlation coefficient (R2) and root mean square error (RMSE) for train set for GA-PLS were (R2 = 0.734, RMSE train = 0.26).
  
  
  CONCLUSIONS
  The predictive ability of the models was found to be satisfactory and could be employed for designing new 1,4-dihydropyridines as potent MDR inhibitors in cancer treatment. 1,4- Dihydropyridine ring containing protonable nitrogen as scaffold could be proposed. Sulfur, ester, amide, acyle, ether, fragments are connected to a 1,4-dihydropyridine ring. Phenyl groups (with an electronegative substituent) as a lipophilic part are essential for the inhibitory effect.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad. Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Mollazadeh
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad. Iran.
authors.forename: Jamal
authors.initials: J
authors.lastname: Shamsara
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran.|Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Iman
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.|Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Farzin
authors.initials: F
authors.lastname: Hadizadeh
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D016018:Least-Squares Analysis; D016014:Linear Models; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004095:Dihydropyridines; C038806:1,4-dihydropyridine
keywords: ATP binding cassette; P-glycoprotein; QSAR; dihydropyridine; docking; multidrug resistance