title: Design and Green Synthesis of Thieno[2,3-d]pyrimidine Analogues as Potential Antiproliferative Agents.
abstract: BACKGROUND
  Despite of significant progress achieved in the chemotherapy of cancer; it is still among the leading cause of morbidity and mortality worldwide.
  
  
  OBJECTIVE
  Taking cognizance of the extensive biological potential of reported thieno[2,3-d]pyrimidines and inspired by the clinically available anticancer agents dasatinib and gefitinib, 4-substituted thieno[2,3-d]pyrimidines have been synthesized.
  
  
  METHODS
  The compounds were synthesized via microwave-assisted methods and screened for their cytotoxic activity against liver HepG-2, lung NCI-H522, melanoma A-375, pancreatic MIA PaCa-2 and colon CaCo-2 human cancer cell lines using MTT assay.
  
  
  RESULTS
  The antiproliferative potential of most active compounds 20b and 20f (piperidino substituted); and 22d (hybrid analogue of Dasatinib) was further assessed and confirmed by calcein AM and colony formation assay, which revealed the higher potency of hybrid analogue 22d in comparison to piperidino substituted derivative 20f.
  
  
  CONCLUSIONS
  Flow cytometer based cell cycle perturbation experiments revealed that antiproliferative effects of the most active compound 22d was associated with increased proportion of cells in the G2/M and subG0/G1 phases of the cell cycle. In silico ADME studies also confer the drug like characteristics of the potent compounds.
authors.affiliation: Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga-142001, Punjab, India.
authors.forename: Rupinder Kaur
authors.initials: RK
authors.lastname: Gill
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska. United States.
authors.forename: Virender
authors.initials: V
authors.lastname: Kumar
authors.affiliation: National Agri-Food Biotechnology Institute, SAS Nagar, Mohali-160071, Punjab, India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Bishnoi
authors.affiliation: National Agri-Food Biotechnology Institute, SAS Nagar, Mohali-160071, Punjab, India.
authors.forename: Kamalendra
authors.initials: K
authors.lastname: Yadav
authors.affiliation: National Agri-Food Biotechnology Institute, SAS Nagar, Mohali-160071, Punjab, India.
authors.forename: Kanthi Kiran
authors.initials: KK
authors.lastname: Kondepudi
authors.affiliation: Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga-142001, Punjab, India.
authors.forename: Jitender
authors.initials: J
authors.lastname: Bariwal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; C000601850:thieno(2,3-d)pyrimidine
keywords: 3-d]pyrimidines; Microwave irradiation; antiproliferative; calcein AM assay; cell cycle analysis; colony formation assay; thieno[2