Facile Synthesis of (R,R) and of (R,S) Tricarballylic Acid Anhydride and Imide Derivatives

The diastereomeric mixture of (R)-2-(methoxycarbonylmethyl)-N-(R)-1-(1-phenylethyl) succinimide 11s and (S)-2-(methoxycarbonylmethyl)-N-(R)-1-(1-phenylethyl) succinimide 11a was synthesized by reaction of 2-(carboxymethyl)succinic anhydride 6 with (R)-(α)-methylbenzylamine in dry THF/room temperature/24 hrs. The diastereomeric mixture of 1-[(R)-(α)-Methylbenzylamideformyl)]propane-2,3-dicarboxylic acid anhydride 9s and 1-[(R)-(α)-methylbenzylamideformyl)]propane-2,3-dicarboxylic acid anhydride 9a was isolated as an intermediate under the reaction conditions. This diastereomeric mixture 9s/9a was also prepared by a different route via reaction of 1-(chloroformyl)propane-2,3-dicarboxylic acid anydride 12 with (R)-(α)-methylbenzylamine in the presence of DMA at 0oC for 24 hrs

Newly Synthesized Palladium (II) Complex ASH10 Induces Apoptosis and Autophagy in Breast Cancer Cells

Background and Objective: Palladacycles have been reported to exert significant anticancer activities against different cancer cells. The current study conducted to evaluate the anti-tumor activity of a new palladacycle complex (ASH10) in estrogen receptor-positive (MCF7) and triple-negative (HCC1937) breast cancer cells. Materials and Methods: The effect of ASH10 on cell proliferation was tested by MTT assay. Scratch assay was used to test the anti-migration ability of ASH10. Apoptosis induced by ASH10 was measured by different methods including nuclear staining and detection of apoptosis markers by western blotting. Autophagy induced by ASH10 also measured by LC3II puncta staining and western blotting using the LC3II antibody. Results: The MTT results showed that the ASH10 compound has a strong anti-growth effect. Data showed that ASH10 induces its cytotoxic effect by inducing DNA damage followed by cell cycle arrest, intrinsic apoptosis and autophagy. Compared to untreated cells, ASH10 treated cells showed high levels of DNA damage markers p-H2AX, p-ATM and p53. Importantly, the cell cycle arrest marker p21 was similarly induced by ASH10 treatment. Furthermore, ASH10 induced significant levels of apoptosis as evidenced by nuclear fragmentation and an increase in the levels of PARP cleavage. Interestingly, ASH10 also activated the formation of autophagosomes and increased the autophagy marker LC3II. Inhibition of autophagy led to a decrease in ASH10 cytotoxicity suggesting that ASH10 induced autophagy was a cytotoxic mechanism. Conclusion: These results demonstrated that ASH10 is a potential effective compound in the treatment of both ER-negative and ER-positive breast cancer cells.Background and Objective: Palladacycles have been reported to exert significant anticancer activities against different cancer cells. The current study conducted to evaluate the anti-tumor activity of a new palladacycle complex (ASH10) in estrogen receptor-positive (MCF7) and triple-negative (HCC1937) breast cancer cells. Materials and Methods: The effect of ASH10 on cell proliferation was tested by MTT assay. Scratch assay was used to test the anti-migration ability of ASH10. Apoptosis induced by ASH10 was measured by different methods including nuclear staining and detection of apoptosis markers by western blotting. Autophagy induced by ASH10 also measured by LC3II puncta staining and western blotting using the LC3II antibody. Results: The MTT results showed that the ASH10 compound has a strong anti-growth effect. Data showed that ASH10 induces its cytotoxic effect by inducing DNA damage followed by cell cycle arrest, intrinsic apoptosis and autophagy. Compared to untreated cells, ASH10 treated cells showed high levels of DNA damage markers p-H2AX, p-ATM and p53. Importantly, the cell cycle arrest marker p21 was similarly induced by ASH10 treatment. Furthermore, ASH10 induced significant levels of apoptosis as evidenced by nuclear fragmentation and an increase in the levels of PARP cleavage. Interestingly, ASH10 also activated the formation of autophagosomes and increased the autophagy marker LC3II. Inhibition of autophagy led to a decrease in ASH10 cytotoxicity suggesting that ASH10 induced autophagy was a cytotoxic mechanism. Conclusion: These results demonstrated that ASH10 is a potential effective compound in the treatment of both ER-negative and ER-positive breast cancer cells

A second polymorph of (Z)-3-amino-4-(2-phenylhydrazinylidene)-1H-pyrazol-5(4H)-one

The molecule of the title compound, C9H9N5O, is approximately planar (the r.m.s. deviation of all non-H atoms is 0.08 Å). The amine substituent is pyramidal at the N atom. An intramolecular N—Hhydrazine...O=C hydrogen bond is present. In the crystal, molecules are connected via N—H...N and N—H...O hydrogen bonds, forming infinite layers parallel to (010). This polymorph is triclinic, space group P-1, whereas the previously reported form was monoclinic, space group P21/c [Elgemeie et al. (2013). Acta Cryst. E69, o187], with stepped layers and a significantly lower density

Ethyl 5-amino-1-[(4-methylphenyl)sulfonyl]-1H-pyrazole-4-carboxylate

In the title molecule, C13H15N3O4S, the benzene and pyrazole rings are inclined to each other at 77.48 (3)°. Two amino H atoms are involved in bifurcated hydrogen bonds, viz. intramolecular N—H...O and intermolecular N—H...O(N). The intermolecular hydrogen bonds link the molecules related by translation in [100] into chains. A short distance of 3.680 (3) Å between the centroids of benzene and pyrazole rings from neighbouring molecules shows the presence of π–π interactions, which link the hydrogen-bonded chains into layers parallel to the ab plane