Synthesis and biological evaluation of anthra[1,9-cd]pyrazol-6(2H)-one scaffold derivatives as potential anticancer agents

Abstract

Severalanthrapyrazolone derivatives derived from 7-chloroanthra [1,9-cd]pyrazol-6(2H)-one and 7-chloro-2-(2-hydroxyethyl)anthra [1,9-cd] pyrazol-6(2H)-one have been prepared by addition or substitution nucleophylic reactions and further transformed into extended tetracyclic systems and fused to different nitrogenheterocyclic rings into the pharmacophore structure moiety. The compounds synthesized were evaluated for their cytotoxic activity and telomerase activity in prostate cancer cell line by SRB assay and in human non-small cell lung carcinoma cell line by TRAP assay, respectively. Compounds 1-6, 13, 14, 16, 17, 19, 21, 23, 28 and 31 were selected by the NCI and only 1, 4, and 16 represent the GI 50 , TGI and LC 50 , respectively. Among them, 1 and 16 exhibited distinctive selectivity of GI 50 of 10.498 μ M and 4.542 μ M over 60 cell lines which better than the average GI 50 (20.3 μ M) for SP600125 (NSC75890). Overall, the test compounds exhibited different telomerase and cytotoxic activities and only few compounds displayed antitumor activity in the low range.

Bis(chloroacetamidino)-Derived Heteroarene-Fused Anthraquinones Bind to and Cause Proteasomal Degradation of tNOX, Leading to c-Flip Downregulation and Apoptosis in Oral Cancer Cells

“…Column chromatography followed by treatment with 1N HCl in methanol was used to obtain water-soluble hydrochloride salts of 2a-c. The assigned structures of 2a-c were confirmed by 1 H and 13 C NMR; the purity of the final samples was >95% (Figure S1 in Supplementary Materials).…”

“…Melting points were determined using a Buchi SMP-20 apparatus and are given uncorrected. 1 H and 13 C NMR spectra were recorded on a Varian Mercury 400 Plus instrument operated at 400 MHz and 100 MHz, respectively. Chemical shifts were measured in DMSO-d 6 using tetramethylsilane as an internal standard.…”

“…Biological investigations revealed that these compounds target various molecules that are essential for tumor progression, including different secondary structures of nucleic acids, DNA topoisomerases, HDAC-6, and others [6][7][8][9][10][11][12]. Among the new-generation compounds, heterocyclic derivatives of anthraquinone are considered to be one of the most promising classes for the analogbased drug design of anticancer compounds [13][14][15]. In particular, the annellation of five-membered heterocycles with one heteroatom to 1,4-diaminoanthraquinone (an analog of mitoxantrone) yielded derivatives that retained a powerful antiproliferative profile and exhibited significantly greater activity against MDR-positive tumor cells [16].…”

Recent Reports on Pyrazole-Based Bioactive Compounds as Candidate for Anticancer Agents

“…Cancer is a group of various diseases, i.e., lung cancer, cervical cancer, prostate cancer, and breast cancer, and all of them are characterized by an abnormal control of cell growth [19]. Despite many clinically successful anticancer drugs have been developed either natural products or synthetic derivatives of naturally occurring lead compounds, there are still limitations in the treatment of cancer including the effectiveness of drugs and serious side effects [20]. Hence, many pyrazole-based compounds have been synthesized and screened by scientists.…”

QSAR Study of Anthra[1,9-cd]pyrazol-6(2H)-one Derivatives as Potential Anticancer Agents Using Statistical Methods

“…In the present study, we chose 32 substitutions of anthra[1,9-cd]pyrazol-6(2H)-one for which their anticancer activities are reported in the literature by Chen et al [24]. On the other side and for the 2DQSAR study, the reported values of IC50 have been converted into PIC50 by taking negative logarithm (PIC50 = log 10 IC50) and subsequently used as the dependent variable for the 3D-QSAR model development.…”