Microwave-Assisted Synthesis of Imidazo[4,5-f][1,10]phenanthroline Derivatives as Apoptosis Inducers in Chemotherapy by Stabilizing Bcl-2 G-quadruplex DNA.

Herein, a series of imidazo[4,5-f][1,10] phenanthroline derivatives RPIP (PIP = imidazo [4,5-f][1,10] phenanthroline, R = NO2, 1; CF3, 2; Cl, 3; OH, 4) have been synthesized in yields of 82.3-94.7% at 100 °C under the irradiation of microwave. MTT assay has been utilized to evaluate the inhibitory activity (IC50) of these compounds against the growth of various tumor cells, and the results revealed that these compounds, especially 1, exhibited excellent inhibitory activity against the growth of A549 cells with IC50 of 15.03 µM. Moreover, it's also confirmed that 1 can penetrate into the membrane of tumor cells and distribute in mitochondria when observed under microscopy, resulting apoptosis of tumor cells. The further studies showed that 1 can bind to bcl-2 G-quadruplex DNA, which demonstrated by the increase of melting point of bcl-2 G4 DNA in the presence of 1, as well as electronic titration and emission spectra. In a word, this kind of compound may develop as a potential apoptosis inducer in cancer chemotherapy via binding and stabilizing to the bcl-2 G-quadruplex DNA.

Chiral Ru(ii) complexes act as a potential non-viral gene carrier for directional transportation to the nucleus and cytoplasm.

Guanine-rich DNA sequences can spontaneously fold into four-stranded structures called G-quadruplexes (G4s). G4s have been identified extensively in the promoter regions of several proto-oncogenes, including c-myc, as well as telomeres. G4s have attracted an increasing amount of attention in the field of nanotechnology because of their use as versatile building blocks of DNA-based nanostructures. In this study, we report the self-assembly of c-myc G-quadruplex DNA controlled by a pair of chiral ruthenium(ii) complexes coordinated by 2-(4-phenyacetylenephenyl)-1H-imidazo[4,5f][1,10]phenanthroline (PBEPIP), Λ-[Ru(bpy)2(PBEPIP)](ClO4)2 (Λ-RM0627, bpy = bipyridine) and Δ-[Ru(bpy)2(PBEPIP)](ClO4)2 (Δ-RM0627). Λ-RM0627 could promote the high-order self-assembly of c-myc G-quadruplex DNA into a nanowire structure, whereas Δ-RM0627 could induce DNA condensation into G-quadruplex aggregates. Moreover, in vitro studies on human liver carcinoma HepG2 cells showed that the nanowire of c-myc G-quadruplex DNA promoted by Λ-RM0627 could be localized in the nuclei of cells, whereas the nanoparticle of c-myc G-quadruplex DNA generated by Δ-RM0627 was taken up and localized in the cytoplasm. This study provides examples of the enantioselective self-assembly of G4 DNA molecules controlled by chiral ruthenium(ii) complexes and suggests the potential applications of assembled nanostructures as non-viral DNA vectors for gene therapy.

A case of unplanned pregnancy at 2 months after uterine curettage in a patient with a hydatidiform mole.

Whether an unplanned pregnancy should be terminated during follow-up of a hydatidiform mole is controversial. We report a patient who had an unplanned pregnancy with a hydatidiform mole at 2 months after uterine curettage when the human chorionic gonadotropin level had decreased to a negative value. Hydatidiform mole was confirmed by histopathology. Uterine curettage was performed twice and regular follow-ups were performed after surgery. The patient achieved a full-term pregnancy. The Apgar score of the newborn was 10 at 1, 5, and 10 minutes, and the newborn had no malformations. We conclude that the pregnancy outcome might be good in an unplanned pregnancy when the human chorionic gonadotropin level is negative.

Rare case of uterine neoplasm: cervical sarcoma with endometrial carcinoma.

Multiple primary malignant tumors (MPMTs) refer to two or more primary malignant neoplasms that simultaneously or successively occur in one or more organs in the same individual. Cervical sarcoma concomitant with endometrial carcinoma is rare. A 46-year-old woman was admitted because of increased menstrual volume for 4 years and irregular vaginal bleeding with discharge for 6 months. The diagnosis of endometrial carcinoma at stage II was made on the basis of results of ultrasound, pelvic magnetic resonance imaging, and hysteroscopic curettage. Extensive total abdominal hysterectomy + bilateral adnexectomy + bilateral ovarian arteriovenous high ligation + pelvic adhesion separation + pelvic lymphadenectomy +abdominal aortic lymphadenectomy via the abdomen were performed. Postoperative diagnosis of cervical sarcomas with endometrial carcinoma in stage IIIC1 was made according to the results of pathology and immunohistochemistry. Six cycles of cisplatin-epirubicin-isocyclophosphamide treatment were provided after the operation. Most clinical manifestations of cervical sarcomas are abnormal vaginal bleeding. Use of preoperative imaging and hysteroscopy is difficult for diagnosing cervical sarcomas, and postoperative pathological examinations and immunohistochemical diagnosis are mainly used instead. The possibility of MPMTs should be considered for endometrial carcinoma, especially if the cervical lesion is larger than that of the uterine cavity.

A phenanthroline derivative enhances radiosensitivity of hepatocellular carcinoma cells by inducing mitochondria-dependent apoptosis.

Combining radiosensitizers with ionizing radiation (IR) is an effective strategy to increase the radiation therapeutic effect for hepatocellular carcinoma (HCC) patients. A phenanthroline derivative, 2-phenyl-imidazo [4, 5 f] [1, 10] phenanthroline (L02), had been synthesized. This study investigated the radiosensitization and mechanisms of L02 combined with IR against HCC. The radiosensitization of L02 combined with IR was evaluated by the sensitivity enhancement ratio (SER) and the isobolographic analysis. The toxicity of L02 and cisplatin were compared by the zebrafish model. The cell cycle and apoptosis were examined by flow cytometry. DNA damage was measured by comet assay and the expressions of apoptosis related proteins were analyzed by western blotting. L02 was effective in sensitizing HCC to IR. The SERs in HepG2 and BEL7402 were 1.41 and 1.28, respectively. The sensitization of L02 was comparable with cisplatin. L02 treatment with IR had synergistic anti-tumor effect. L02 enhanced the percentage of IR induced apoptosis cells. L02 increased comet tail in comet assay when combined with IR. L02 sensitized HCC to IR by the activation of P53 signaling, the decrease in Bcl-2, up-regulation of cytochrome c and the subsequent activation of caspase-3. L02 sensitizes HCC to IR, mostly likely by inhibiting cell proliferation, inducing DNA damage and mitochondria-dependent apoptosis. L02 may be a novel radiosensitizer for HCC.

Preparation of Ru(ii)@oligonucleotide nanosized polymers as potential tumor-imaging luminescent probes.

The development of Ru(ii) complexes as luminescent probes has attracted increasing attention in recent decades. In this study, the nanosized polymers of two Ru(ii) complexes [Ru(phen)2(dppz)](ClO4)2 (1, phen = 1,10-phenanthrolin; dppz = dipyrido[3,2-a:2',3'-c]phenazine) and [Ru(phen)2(Br-dppz)](ClO4)2 (2, Br-dppz = 11-bromodipyrido[3,2-a:2',3'-c]phenazine) with oligonucleotides were prepared and investigated as potential tumor-imaging probes. The formation of the nanosized polymers, which had an average width of 125-438 nm and an average height of 3-6 nm, for 1 and 2@oligonucleotides were observed through atomic force microscopy. The emission spectra indicated that the luminescence of 1 and 2 markedly increased after binding to oligonucleotides and double-strand DNA (calf thymus DNA), respectively. Moreover, further studies indicated that 1@oligonucleotides and 2@oligonucleotides can easily enter into tumor cells and selectively highlight the tumor area in the zebrafish bear xenograft tumor (MDA-MB-231). In summary, this study demonstrated that 1@oligonucleotides and 2@oligonucleotides could be developed as potential tumor-imaging luminescent probes for clinical diagnosis and therapy.

A three-dimensional zinc-based coordination polymer built from 5-carboxylato-1-carboxylatomethyl-2-oxidopyridinium with a 4-connected sra topology.

A novel three-dimensional Zn(II) complex, poly[aqua(µ4-5-carboxylato-1-carboxylatomethyl-2-oxidopyridinium)zinc(II)], [Zn(C8H5NO4)(H2O)]n, has been prepared by hydrothermal assembly of Zn(CH3COO)2·2H2O and 5-carboxy-1-(carboxymethyl)pyridin-1-ium-2-olate (H2ccop). The ccop(2-) anions bridge the Zn(II) cations in a head-to-tail fashion via monodentate aromatic carboxylate and phenolate O atoms to form an extended zigzag chain which runs parallel to the [011] direction. One O atom of the aliphatic carboxylate group of the ccop(2-) ligand coordinates to the Zn(II) atom of a neighbouring chain thereby producing undulating layers which lie parallel to the (01-1) plane. A similar parallel undulating planar structure can be obtained if a path involving the other O atom of the aliphatic carboxylate group is considered. Thus, the aliphatic carboxylate group acts in a bridging bidentate mode to give extended -Zn-O-C-O-Zn- sequences running parallel to [001] which link the layers into an overall three-dimensional framework. The three-dimensional framework can be simplified as a 4-connected sra topology with a Schläfli symbol of 4(2).6(3).8 if all the Zn(II) centres and ccop(2-) anions are regarded as tetrahedral 4-connected nodes. The three-dimensional luminescence spectrum was measured at room temperature with excitation and emission wavelengths of 344-354 and 360-630 nm, respectively, at intervals of 0.15 and 2 nm, respectively.