👤 Tan MX

In the era of high throughput sequencing, special software is required for the clinical evaluation of genetic variants. We developed REEV (Review, Evaluate and Explain Variants), a user-friendly platform for clinicians and researchers in the field of rare disease genetics. Supporting data was aggregated from public data sources. We compared REEV with seven other tools for clinical variant evaluation. REEV (semi-)automatically fills individual ACMG criteria facilitating variant interpretation. REEV can store disease and phenotype data related to a case to use these for phenotype similarity measures. Users can create public permanent links for individual variants that can be saved as browser bookmarks and shared. REEV may help in the fast diagnostic assessment of genetic variants in a clinical as well as in a research context. REEV (https://reev.bihealth.org/) is free and open to all users and there is no login requirement. Show less

Title: In vitro and in vivo anticancer activity of novel Rh(III) and Pd(II) complexes with pyrazolopyrimidine derivatives. Abstract: Six pyrazolopyrimidine rhodium(III) or palladium(II) complexes, [Rh(L1)(H2O)Cl3] (1), [Rh(L2)(CH3OH)Cl3] (2), [Rh(L3)(H2O)Cl3] (3), [Rh2(L4)Cl6]·CH3OH (4), [Rh(L5)(CH3CN)Cl3]·0.5CH3CN (5), and [Pd(L5)Cl2] (6), were synthesized and characterized. These complexes showed high cytotoxicity against six tested cancer cell lines. Most of the complexes showed higher cytotoxicity to T-24 cells in vitro than cisplatin. Mechanism studies indicated that complexes 5 and 6 induced G2/M phase cell cycle arrest through DNA damage, and induced apoptosis via endoplasmic reticulum stress response. In addition, complex 5 also induced cell apoptosis via mitochondrial dysfunction. Complexes 5 and 6 showed low in vivo toxicity and high tumor growth inhibitory activity in mouse tumor models. The inhibitory effect of rhodium complex 5 on tumor growth in vivo was more pronounced than that of palladium complex 6. Show less

Title: Rhodium(III)-Picolinamide Complexes Act as Anticancer and Antimetastasis Agents via Inducing Apoptosis and Autophagy. Abstract: As a continuation of our endeavors in discovering metal-based drugs with cytotoxic and antimetastatic activities, herein, we reported the syntheses of 11 new rhodium(III)-picolinamide complexes and the exploration of their potential anticancer activities. These Rh(III) complexes showed high antiproliferative activity against the tested cancer cell lines in vitro. The mechanism study indicated that Rh1 ([Rh(3a)(CH3CN)Cl2]) and Rh2 ([Rh(3b)(CH3CN)Cl2]) inhibited cell proliferation by multiple modes of action via cell cycle arrest, apoptosis, and autophagy and inhibited cell metastasis via FAK-regulated integrin β1-mediated suppression of EGFR expression. Furthermore, Rh1 and Rh2 significantly inhibited bladder cancer growth and breast cancer metastasis in a xenograft model. These rhodium(III) complexes could be developed as potential anticancer agents with antitumor growth and antimetastasis activity. Show less

Three novel Ru(II) complexes, namely, (RuCl₂[L^a][DMSO]₂)·H₂O (Ru1), (RuCl₂[L^b][DMSO]₂) (Ru2), and (RuCl₂[L^c][DMSO]₂) (Ru3), which respectively contain 3-(2'-benzimidazolyl)coumarin (L^a), 3-(2'-benzimidazolyl)-7-fluoro-coumarin (L^b), and 3-(2'-benzimidazolyl)-7-methoxyl-coumarin (L^c), were first designed and characterized. Ru2 showed potent antitumor activity against NCI-H460 cells (IC₅₀ = 0.30 ± 0.02 μM) and high selectivity between NCI-H460 cancer cells and normal HL-7702 cells. Ru2 induced NCI-H460 apoptosis via telomerase inhibition, which involved DNA damage, cell-cycle distribution, and S phase-protein down-regulation. However, Ru1 did not demonstrate such effects in NCI-H460 cells, which is undoubtedly associated with the key regulatory role of the 7-fluoro substituted group in the L^b ligand of Ru2. Ru2 exhibited considerably higher anticancer efficacy (inhibition rate [IR] = 61.3%) compared with cisplatin (IR= 25.5%) in a NCI-H460 xenograft mouse model. Thus, this coumarin Ru(II) compound is a promising Ru2-targeting telomerase anticancer agent. Show less

Herein, six ruthenium(ii) terpyridine complexes, i.e. [RuCl₂(4-EtN-Phtpy)(DMSO)] (Ru1), [RuCl₂(4-MeO-Phtpy)(DMSO)] (Ru2), [RuCl₂(2-MeO-Phtpy)(DMSO)] (Ru3), [RuCl₂(3-MeO-Phtpy)(DMSO)] (Ru4), [RuCl₂(1-Bip-Phtpy)(DMSO)] (Ru5), and [RuCl₂(1-Pyr-Phtpy)(DMSO)] (Ru6) with 4'-(4-diethylaminophenyl)-2,2':6',2''-terpyridine (4-EtN-Phtpy), 4'-(4-methoxyphenyl)-2,2':6',2''-terpyridine (4-MeO-Phtpy), 4'-(2-methoxyphenyl)-2,2':6',2''-terpyridine (2-MeO-Phtpy), 4'-(3-methoxyphenyl)-2,2':6',2''-terpyridine (3-MeO-Phtpy), 4'-(1-biphenylene)-2,2':6',2''-terpyridine (1-Bip-Phtpy), and 4'-(1-pyrene)-2,2':6',2''-terpyridine (1-Pyr-Phtpy), respectively, were synthesized and fully characterized. The MTT assay demonstrates that the in vitro anticancer activity of Ru1 is higher than that of Ru2-Ru6 and more selective for Hep-G2 cells than for normal HL-7702 cells. In addition, various biological assays show that Ru1 and Ru6, especially the Ru1 complex, are telomerase inhibitors targeting c-myc G4 DNA and also cause apoptosis of Hep-G2 cells. With the same Ru center, the in vitro antitumor activity and cellular uptake ability of the 4-EtN-Phtpy and 1-Bip-Phtpy ligands follow the order 4-EtN-Phtpy > 1-Bip-Phtpy. Show less

There iridium(III) complexes, [Ir(3-MeO-Phtpy)Cl₃] (1), [Ir(2-MeO-Phtpy)Cl₃] (2) and [Ir(4-MeO-Phtpy)Cl₃] (3) with 4'-(3-methoxyphenyl)-2,2':6',2″-terpyridine (3-MeO-Phtpy), 4'-(2-methoxyphenyl)-2,2':6',2″-terpyridine (2-MeO-Phtpy) and 4'-(4-methoxyphenyl)-2,2':6',2″-terpyridine (4-MeO-Phtpy) as ligands, respectively, were synthesized and evaluated for their antiproliferative activities. In these complexes, the iridium(III) center adopts a six-coordinate distorted octahedral geometry. Among them, complex 1 exhibited the most potent activity, with IC₅₀ values of 3.19-27.77 μM against four cancer cell lines (BEL-7404, Hep-G2, NCI-H460 and MGC80-3 cells). Cellular mechanism studies suggested that complexes 1-3 directly targeted c-myc promoter elements and inhibited the telomerase activity. In addition, complexes 1-3 may trigger cell apoptosis via a mitochondrial dysfunction pathway. We postulated that the difference in the in vitro antitumor activities of complexes 1-3 is mainly dependent on the position of the methoxy group on the phenyl ring of the iridium ligand. Show less