Enhancer of zeste homolog 2 (EZH2) is a candidate oncogenic driver due to its prevalent overexpression and aberrant repression of tumor suppressor genes in diverse cancers. Therefore, blocking EZH2 enzyme activity may present a valid therapeutic strategy for the treatment of cancers with EZH2 overexpression including breast cancers. Here, we described ZLD1039 a potent, highly selective, and orally bioavailable small molecule inhibitor of EZH2, which inhibited breast tumor growth and metastasis. ZLD1039 considerably inhibited EZH2 methyltransferase activity with nanomolar potency, decreased global histone-3 lysine-27 (H3K27) methylation, and reactivated silenced tumor suppressors connected to increased survival of patients with breast cancer. Comparable to conditional silencing of EZH2, its inhibition by ZLD1039 decreased cell proliferation, cell cycle arrest, and induced apoptosis. Comparably, treatment of xenograft-bearing mice with ZLD1039 led to tumor growth regression and metastasis inhibition. These data confirmed the dependency of breast cancer progression on EZH2 activity and the usefulness of ZLD1039 as a promising treatment for breast cancer.

Three biomimetic 2Fe2S complexes [{(micro-SCH2)2NCH2(2-C4H3O)}](Fe2(CO)6), [{(micro-SCH2)2 NCH2(2-C4H3S)}](Fe2(CO)6) and [{(micro-SCH2)2NCH2(5-Br-2-C4H2S)}Fe2(CO)6] were prepared as models for the active site of Fe-only hydrogenase by the convergent process from [(micro-S2)Fe2(CO)6] and N,N-bis(hydromethyl)-2-furan and thiophene. The structures of these complexes were identified spectroscopically and crystallographically. The electrochemical behavior of the complexes and was unique as they showed catalytic proton reduction with a low reduction potential at -1.13 and -1.09 V vs Fc/Fc+, respectively, in the presence of HClO4.

New chemotherapeutic compounds are needed to combat multidrug-resistant Mycobacterium tuberculosis (Mtb), which remains a serious public-health challenge. Decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1 enzyme) has been characterized as an attractive therapeutic target to address this urgent demand. Herein, we have identified a new class of DprE1 inhibitors benzothiazinethiones as antitubercular agents. Benzothiazinethione analogue SKLB-TB1001 exhibited excellent activity against Mtb in the Microplate Alamar blue assay and intracellular model, meanwhile SKLB-TB1001 was also highly potent against multi-drug resistant extensively and drug resistant clinical isolates. Importantly, no antagonism interaction was found with any two-drug combinations tested in the present study and the combination of SKLB-TB1001 with rifampicin (RMP) was proved to be synergistic. Furthermore, benzothiazinethione showed superb in vivo antitubercular efficacy in an acute Mtb infection mouse model, significantly better than that of BTZ043. These data combined with the bioavailability and safety profiles of benzothiazinethione indicates SKLB-TB1001 is a promising preclinical candidate for the treatment of drug-resistant tuberculosis.

A microwave-assisted regioselective reaction dealing with arylglyoxal monohydrate, diverse N-aryl enaminones, and indoles to achieve 3,2'- and 3,3'-bis-indoles by varying a substituted indole substrate is reported. The 2-unsubstituted indoles resulted in the 3,2'-bis-indole skeleton, whereas indoles bearing a methyl or phenyl group at C2 led to the 3,3'-bis-indoles with simultaneous formation of three sigma-bonds. The procedures feature excellent regioselectivity, short reaction times, convenient one-pot manner, and operational simplicity.

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