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.

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.

Carbohydrate-conjugate heterobimetallic complexes: synthesis, DNA binding studies, artificial nuclease activity and in vitro cytotoxicity.

New carbohydrate-conjugated heterobimetallic complexes [C(32)H(62)N(10)O(8)NiSn(2)Cl(4)]Cl(2)(1) and [C(32)H(62)N(10)O(8)CuSn(2)Cl(4)]Cl(2) (2) were synthesized and characterized by spectroscopic (IR, (1)H, (13)C, and (119)Sn NMR, EPR, UV-vis, ESI-MS) and analytical methods. The interaction studies of 2 with CT DNA were studied by using various biophysical techniques, which showed high binding affinity of 2 toward CT DNA. The extent of interaction was further confirmed by the interaction of 2 with the nucleotides viz.; 5'-AMP, 5'-CMP, 5'-GMP, and 5'-TMP, by absorption titration. (1)H, (31)P, (119)Sn NMR spectroscopy further validated the interaction mode of 2 with 5'-GMP. The electrophoresis pattern observed for 2 with supercoiled pBR322 DNA, exhibited significantly good nuclease activity following oxidative pathway. The preferential selectivity of 2 toward the major groove was observed on interaction of 2 with pBR322 DNA, in the presence of standard groove binders viz.; DAPI and methyl green. Additionally, in vitro antitumor activity of 2 was evaluated on a panel of human cancer cell lines, exhibiting remarkable cytotoxicity activity against Colo205 (colon) and MCF7 (breast) cell lines with GI(50) values <10 µg/mL.

Synthesis of carbohydrate-conjugate heterobimetallic Cu(II)-Sn(2)(IV) and Zn(II)-Sn(2)(IV) complexes; their interactions with CT DNA and nucleotides; DNA cleavage, in-vitro cytotoxicity.

The new heterobimetallic Ni(II)-Sn(2)(IV) (1), Cu(II)-Sn(2)(IV) (2) and Zn(II)-Sn(2)(IV) (3) complexes, containing D-glucosamine, 1,8-diamino-3,6-diazaoctane and imidazole were isolated and characterized by spectral and analytical methods. The proposed geometry of Ni(II) and Cu(II) in 1 and 2 was square pyramidal, Zn(II) in 3 exhibited tetrahedral while Sn(IV) exhibits hexacoordinate environment, respectively. The X-ray powder diffraction (XRPD) confirmed the amorphous nature of all the complexes. The interaction studies of 2 and 3 with CT DNA were carried out by various biophysical techniques to show the mode of binding. The interaction of 2 and 3 with nucleotides viz 5'-GMP and 5'-TMP, respectively were further confirmed by (1)H, (31)P and (119)Sn NMR spectroscopy. The complex 2 exhibited effective cleavage activity with pBR322 DNA. Furthermore, the cytotoxicity of 2 was examined on a panel of human tumor cell lines of different histological origins and showed good activity against Colo205 and A2780 (GI50 < 10 µg/ml).

Remarkable DNA binding affinity and potential anticancer activity of pyrrolo[2,1-c][1,4]benzodiazepine-naphthalimide conjugates linked through piperazine side-armed alkane spacers.

A series of pyrrolobenzodiazepine-naphthalimide conjugates tethered through a piperazine ring system have been designed, synthesized, and evaluated for their anticancer activity. These new conjugates exhibit very high DNA binding affinity and cytotoxic activity against a number of cell lines.

Phosphonate-linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates: synthesis, DNA-binding affinity and cytotoxicity.

Pyrrolobenzodiazepine-diethylphosphonate conjugates have been designed and synthesized that link through two different types of spacers that are simple alkane chain and also a piperazine moiety side-armed with the alkane chains. These pyrrolobenzodiazepine conjugates have exhibited remarkable DNA-binding affinity and improved solubility in water, a representative compound 7d showing promising in vitro cytotoxicity.

Synthesis, DNA binding, and cytotoxicity studies of pyrrolo[2,1-c][1,4]benzodiazepine-anthraquinone conjugates.

A series of pyrrolo[2,1-c][1,4]benzodiazepine-anthraquinone conjugates have been prepared and evaluated for their DNA binding ability as well as anticancer activity. Some of these molecules have shown significant anticancer activity in a number of cancer cell lines.