title: Synthesis, Molecular Docking Study and in vitro Anticancer Activity of Tetrazole Linked Benzochromene Derivatives.
abstract: BACKGROUND
  Globally, cancer is regarded as one of the biggest health concern in humans and animals and is one of the most terrifying diseases. Therefore, there is a necessity for the discovery, development and improvement of novel antitumor drug molecules which could efficiently prevent proliferative pathways and clonal expansion of cells. Heterocyclic compounds like benzochromene play a key role in the development of current pharmaceuticals, natural resources, agriculture products, analytical reagents and dyes. Therefore, anticancer drugs show increased resistance, it is essential to designing the novel structured heterocyclic moieties to create potential anticancer agents with promising biological applications.
  
  
  OBJECTIVE
  To synthesis a novel 1-(substitutedphenyl)-2-(1H-tetrazol-5-yl)-1H-benzo[f]chromene-3-amine derivatives for in vitro antitumour activity.
  
  
  METHODS
  The reaction of 3-amino-1-(substitutedphenyl)-1H-benzo[f]chromene-2-carbonitrile with sodium azide, ammonium chloride in dimethyl formamide solvent under reflux condition for 4 h afforded products (3a-k). The synthesized molecules were subjected to possible potential anti-tumour activity in vitro in four human cancer cell lines (MCF-7, Caco-2, HeLa and SKBR-3), and one human non-cancer cell line (HEK293), using the MTT cell viability assay.
  
  
  RESULTS
  A novel series of products (3a-k) were synthesized with good yield and were identified with 1H NMR, 15N NMR, 13C NMR, FT-IR and HR-MS spectrum. The most potent compounds 3d, 3e, and 3f possessing the greatest cytotoxicity activity with IC50 values slightly higher (15-33 μM) than that of 5-Fluorouracil (10-17 μM), indicating their potential to be antitumor agents. The 3a, 3b, 3c, 3h, 3i and 3j compounds showed moderate activity. Additionally, a molecular docking analysis was conducted to predict the multi-drug resistance modulator behavior of synthesized compounds in the ATP binding site of P-glycoprotein.
  
  
  CONCLUSIONS
  We synthesized and designated eleven novel derivatives of tetrazole linked benzochromenes (3a-k) and evaluated their anti-cancer activity. Additionally, the results from the docking studies were found to be in good agreement with the results from computational profiling.
authors.affiliation: Non-viral gene delivery laboratory, Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Chiltern Hills, Durban-4000, South Africa.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Gorle
authors.affiliation: Department of Chemistry, School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus, Chiltern Hills, Durban-4000, South Africa.
authors.forename: Suresh
authors.initials: S
authors.lastname: Maddila
authors.affiliation: School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus, Chiltern Hills, Durban-4000, South Africa.
authors.forename: Surya N
authors.initials: SN
authors.lastname: Maddila
authors.affiliation: Non-viral gene delivery laboratory, Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Chiltern Hills, Durban-4000, South Africa.
authors.forename: Kovashnee
authors.initials: K
authors.lastname: Naicker
authors.affiliation: Non-viral gene delivery laboratory, Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Chiltern Hills, Durban-4000, South Africa.
authors.forename: Moganavelli
authors.initials: M
authors.lastname: Singh
authors.affiliation: School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus, Chiltern Hills, Durban-4000, South Africa.
authors.forename: Parvesh
authors.initials: P
authors.lastname: Singh
authors.affiliation: School of Chemistry & Physics, University of KwaZulu-Natal, Westville Campus, Chiltern Hills, Durban-4000, South Africa.
authors.forename: Sreekantha B
authors.initials: SB
authors.lastname: Jonnalagadda
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D013777:Tetrazoles
keywords: ATP binding; Synthesis; benzochromenes; cytotoxicity; docking study; tetrazoles