The Schiff base ligands benzylidene­(4-tert-butylphenyl)­amine 4-methyl ester (L1), (4-nitrobenzylidene)­(4-tert-butylphenyl)­amine (L2), and (4-cyanobenzylidene)­(4-tert-butylphenyl)­amine (L3) and the new series of cyclometalated mononuclear piano-stool complexes [(η5-C5Me5)­RhCl­(L1)] (1), [(η5-C5Me5)­RhCl­(L2)] (2), [(η5-C5Me5)­RhCl­(L3)] (3), [(η5-C5Me5)­IrCl­(L1)] (4), [(η5-C5Me5)­IrCl­(L2)] (5), and [(η5-C5Me5)­IrCl­(L3)] (6) have been synthesized. The ligands L1–L3 and complexes 1–6 have been thoroughly characterized by satisfactory elemental analyses, spectral studies (ESI-MS, IR, 1H and 13C NMR, UV–vis), and structures of 1–3 authenticated by X-ray single-crystal analyses. Efficient binding of 1–6 with calf thymus DNA (CT DNA) have been established by UV–vis and emission spectroscopic studies. Protein binding (bovine serum albumin, BSA) has been investigated by UV–vis, fluorescence, synchronous, and 3D fluorescence spectroscopy. Binding of the complexes with DNA through minor groove and hydrophobic interaction with proteins via sub domain IIA cavity has been substantiated by molecular docking studies. The complexes exhibited significant cytotoxicity against the human lung cancer cell line (A549), and 1 and 2 showed better activity than cisplatin. The cytotoxicity, morphological changes, and apoptosis have been assessed by MTT assay, Hoechst 33342/PI staining, cell cycle analysis by fluorescence-activated cell sorting (FACS), and reactive oxygen species (ROS) generation by DCFH-DA dye. The complexes 1–6 induce apoptosis in the order 2 > 1 > 4 > 3 > 5 > 6.

Background/aimsHypoxia microenvironment plays a crucial role during tumor progression and it tends to exhibit poor prognosis and make resistant to various conventional therapies. HIF-1α acts as an important transcriptional regulator directly or indirectly associated with genes involved in cell proliferation, angiogenesis, apoptosis and energy metabolism during tumor progression in hypoxic microenvironment. This study was aimed to investigate the expression pattern of the hypoxia associated genes and their association during breast cancer progression under hypoxic microenvironment in breast cancer cells.MethodsCell proliferation in MCF-7 and MDA-MB-231 cell lines treated with different concentration of CoCl2 was analyzed by MTT assay. Flow cytometry was performed to check cell cycle distribution, whereas cell morphology was examined by phase contrast microscopy in both the cells during hypoxia induction. Expression of hypoxia associated genes HIF-1α, VEGF, p53 and BAX were determined by semiquantitative RT-PCR and real-time PCR. Western blotting was performed to detect the expression at protein level.ResultsOur study revealed that cell proliferation in CoCl2 treated breast cancer cells were concentration dependent and varies with different cell types, further increase in CoCl2 concentration leads to apoptotic cell death. Further, accumulation of p53 protein in response to hypoxia as compare to normoxia showed that induction of p53 in breast cancer cells is HIF-1α dependent. HIF-1α dependent BAX expression during hypoxia revealed that after certain extent of hypoxia induction, over expression of BAX conquers the effect of anti-apoptotic proteins and ultimately leads to apoptosis in breast cancer cells.ConclusionIn conclusion our results clearly indicate that CoCl2 simulated hypoxia induce the accumulation of HIF-1α protein and alter the expression of hypoxia associated genes involved in angiogenesis and apoptosis.Electronic supplementary materialThe online version of this article (10.1186/s40659-019-0221-z) contains supplementary material, which is available to authorized users.

Syntheses and characterizations of the arene ruthenium [(η(6)-C6H6)RuCl(4-mtdpm)] (1), [(η(6)-p-MeC6H4Pr(i))RuCl(4-mtdpm)] (2), and structurally analogous rhodium/iridium complexes [(η(5)-C5Me5)RhCl(4-mtdpm)] (3) and [(η(5)-C5Me5)IrCl(4-mtdpm)] (4) [4-mtdpm = 5-(4-methylthiophenyl)dipyrromethene] have been reported. Their identities have been established by satisfactory elemental analyses, electrospray ionization-mass spectrometry (ESI-MS), FT-IR, NMR ((1)H, (13)C), UV/vis, emission spectral, and electrochemical studies. Structure of the representative complex 3 has been authenticated by X-ray single crystal analyses. The complexes 1-4 effectively bind with calf thymus DNA (CT DNA) through intercalative/electrostatic interactions. In addition, these exhibit significant cytotoxicity toward Dalton lymphoma (DL) cell line and cause static quenching of the bovine serum albumin (BSA) fluorophore. The antiproliferative activity, morphological changes, and apoptosis have been evaluated by MTT assay, acridine orange/ethidium bromide (AO/EtBr) fluorescence staining, and DNA ladder assay. Mode of interaction of the complexes with DNA/protein has also been supported by molecular docking. Various studies revealed remarkable decrease in the in vitro DL cell proliferation and induction of the apoptosis by 1-4, which lies in the order 2 > 1 > 4 > 3.

Postovulatory aging is associated with several morphological, cellular and molecular changes that deteriorate egg quality either by inducing abortive spontaneous egg activation (SEA) or by egg apoptosis. The reduced egg quality results in poor fertilization rate, embryo quality and reproductive outcome. Although postovulatory aging-induced abortive SEA has been reported in several mammalian species, the molecular mechanism(s) underlying this process remains to be elucidated. The postovulatory aging-induced morphological and cellular changes are characterized by partial cortical granules exocytosis, zona pellucida hardening, exit from metaphase-II (M-II)arrest and initiation of extrusion of second polar body in aged eggs. The molecular changes include reduction of adenosine 3',5'- cyclic monophosphate (cAMP) level, increase of reactive oxygen species (ROS) and thereby cytosolic free calcium (Ca2+) level. Increased levels of cAMP and/or ROS trigger accumulation of Thr-14/Tyr-15 phosphorylated cyclin-dependent kinase 1 (Cdk1) on one hand and degradation of cyclin B1 through ubiquitin-mediated proteolysis on the other hand to destabilize maturation promoting factor (MPF). The destabilized MPF triggers postovulatory aging-induced abortive SEA and limits various assisted reproductive technologies (ARTs) outcome in several mammalian species. Use of certain drugs that can either increase cAMP or reduce ROS level would prevent postovulatory aging-induced deterioration in egg quality so that more number of good quality eggs can be made available to improve ART outcome in mammals including human.

The synthesis of four novel heteroleptic dipyrrinato complexes [(η(6)-arene)RuCl(2-pcdpm)] (η(6)-arene = C6H6, 1; C10H14, 2) and [(η(5)-C5Me5)MCl(2-pcdpm)] (M = Rh, 3; Ir, 4) containing a new chelating ligand 4-(2-methoxypyridyl)-phenyldipyrromethene (2-pcdpm) have been described. The complexes 1-4 have been fully characterized by various physicochemical techniques, namely, elemental analyses, spectral (ESI-MS, IR, (1)H, (13)C NMR, UV/vis) and electrochemical studies (cyclic voltammetry (CV) and differential pulse voltammetry (DPV)). Structures of 3 and 4 have been determined crystallographically. In vitro antiproliferative and cytotoxic activity of these complexes has been evaluated by trypan blue exclusion assay, cell morphology, apoptosis, acridine orange/ethidium bromide (AO/EtBr) fluorescence staining, and DNA fragmentation assay in Dalton lymphoma (DL) cell lines. Interaction of 1-4 with calf thymus DNA (CT DNA) has also been supported by absorption titration and electrochemical studies. Our results suggest that in vitro antitumor activity of 1-4 lies in the order 2 > 1 > 4 > 3.