Cancer 2013 July-14

 

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.

Dalton Trans. 2013 Mar 14;42(10):3390-401.

Arjmand F, Sayeed F, Parveen S, Tabassum S, Juvekar AS, Zingde SM.

Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India. farukh_arjmand@yahoo.co.in

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.

PMID: 23250651

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