title: Design and synthesis of (S)- and (R)-enantiomers of [4-(2-hydroxy-1-phenylethylimino)pent-2-ol]dimethyltin(iv) and 2,2-dimethyl-4-phenyl-1,3,2-oxazastannolidine: in vitro antitumor activity against human tumor cell lines and in vivo assay of (S)-enantiomers.
abstract: New dimethyltin derived antitumor drug candidates (S)- and (R)-[4-(2-hydroxy-1-phenylethylimino)pent-2-ol]dimethyltin(iv), 1 and (S)- and (R)-[2,2-dimethyl-4-phenyl-1,3,2-oxazastannolidine], 2 derived from (R)- and (S)-enantiomers of [4-(2-hydroxy-1-phenylethylimino)pent-2-ol] and 2-amino-2-phenylethanol, respectively, were synthesized and thoroughly characterized. Preliminary complex-DNA interaction studies employing various optical methods revealed that the (S)-enantiomer displayed a higher propensity towards the drug target DNA double helix. This was quantified by K(b) and K(sv) values of ligands L and L' and (S)-/(R)-1 and (S)-/(R)-2 complexes, which demonstrated a multifold increase in the case of the (S)-enantiomers in comparison to their (R)-enantiomeric forms. This clearly demonstrates the chiral preference of the (S)-enantiomer over the (R)-enantiomer, and its potency to act as a chemotherapeutic agent. Therefore, the in vitro antitumor activity of the (S)-enantiomer of 1 and 2 was evaluated by the sulforhodamine-B (SRB) assay to assess cellular proliferation against five different human cell lines viz., Hop62, DWD, K562, DU145 and MCF-7. The complex (S)-1 displayed a remarkably pronounced and specific activity for K562, while complex (S)-2 exhibited significant activity towards Hop62, DWD, DU145 and MCF-7. The in vivo antitumor activity of (S)-1 and (S)-2 was carried out, which revealed significant regression in human lung tumors.
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India. farukh_arjmand@yahoo.co.in
authors.forename: Farukh
authors.initials: F
authors.lastname: Arjmand
authors.forename: Fatima
authors.initials: F
authors.lastname: Sayeed
authors.forename: Shazia
authors.initials: S
authors.lastname: Parveen
authors.forename: Sartaj
authors.initials: S
authors.lastname: Tabassum
authors.forename: Aarti S
authors.initials: AS
authors.lastname: Juvekar
authors.forename: Surekha M
authors.initials: SM
authors.lastname: Zingde
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D008175:Lung Neoplasms / Q000188:drug therapy; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009947:Organotin Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D009994:Osmolar Concentration; D012545:Schiff Bases / Q000737:chemistry; D013237:Stereoisomerism; D017971:Tin Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D014183:Transplantation, Heterologous
chemical_list: C583014:(4-(2-hydroxy-1-phenylethylimino)pent-2-ol)dimethyltin; C583015:2,2-dimethyl-4-phenyl-1,3,2-oxazastannolidine; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009947:Organotin Compounds; D012545:Schiff Bases; D017971:Tin Compounds; D004247:DNA