Synthesis, Characterization, and Biological Evaluation of M(I)(CO)₃(NNO) Complexes (M = Re, ^99mTc) Conjugated to 2-(4-Aminophenyl)benzothiazole as Potential Breast Cancer Radiopharmaceuticals

Abstract

The synthesis and biological evaluation of new M(I)(CO)3(NNO) (M = Re, 99mTc) complexes attached to the antitumor agent 2-(4-aminophenyl)benzothiazole are reported. The fluorescent rhenium complex enters MCF-7 breast cancer cells but does not enter normal HFFF-2 and MRC-5 cells. The analogous radioactive 99mTc complex produces fast blood and soft tissue clearance when administered to healthy mice. These complexes are promising candidates for developing radiopharmaceuticals for imaging (99mTc) and targeted radiotherapy (186Re, 188Re) of breast cancer.

Synthesis and antitumor activity evaluation of new 2-(4-aminophenyl)benzothiazole derivatives bearing different heterocyclic rings

“…Compounds 3,6,8,10,11,12,16,18 and 20 were selected by NCI for 60 human tumor cell lines' anticancer screening test at single dose assay. In vitro single-dose anticancer assay was performed in full NCI 60 cell panel representing L, NSCLC, CC, CNSC, M, OC, RC, PC, and BC.…”

“…Unexpectedly, it was found that, 2-(4-aminophenyl)benzothiazole derivatives inhibit cancer cell growth with nanomolar scale against a large panel of human cancer cell lines particularly against breast, colon and ovarian cell lines in in vitro anticancer screening program of the National Cancer Institute (NCI) with a characteristic biphasic doseresponse relationship 6,7 . Up to present, scientists Shi and Bradshaw have a series of studies on antitumor activity of some benzothiazole derivatives [8][9][10][11][12][13][14] .…”

Exploring EPR Parameters of 99Tc Complexes for Designing New MRI Probes: Coordination Environment, Solvent, and Thermal Effects on the Spectroscopic Properties

“…According to Tzanopoulou et al, Figure 1 is a potential candidate for imaging techniques ( 99m Tc), facilitating breast cancer diagnosis [12,13]. In view of that, we have performed EPR calculations evaluating thermal and solvent effects on the hyperfine coupling constant (HFCC) in Complex 1.…”

“…More recently, radioisotopes of technetium (Tc) have been considered promising nuclei for the NMR (Nuclear Magnetic Resonance) and MRI techniques [9][10][11]. Based on this context, in 2006 Tzanopoulou et al synthesized the ( 99m Tc)(CO) 3 (NNO) complex conjugated to the antitumor agent 2-(4 -aminophenyl)benzothiazole [ABT; see Complex 1, Figure 1] [12]. The ABT compound presents nanomolar activity in vitro against some breast cancer cells in humans.…”

Synthesis and Antitumor Activity Evaluation of New 2-(4-aminophenyl) benzothiazole/oxazole/imidazole Derivatives

“…The structural simplicity and synthetic accessibility of benzothiazole (1)(2)(3)(4) ,benzoxazole and benzimidazole series show remarkable antitumor properties. A series of potent and selective agents derived from 2-(4-Aminophenyl)benzothiazole structure was extensively examined and developed during recent years to have antitumor activity since 1996 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) , Unexpectedly, it was found that , 2-(4-aminophenyl) benzothiazole and related structure derivatives inhibit cancer cell growth with nanomolar scale against a large panel of human cancer cell lines particularly against breast , colon and ovarian cell lines in in-vitro anticancer screening program of the National Cancer Institute (NCI) with a characteristic biphasic dose-response relationship. The original (unsubstituted) member of this series, 2-(4-aminophenyl) benzothiazole was considered to be ''Lead ''approach to drug discovery of new anticancer agents.…”