A dual mode 'turn-on' fluorescence-Raman (SERS) response probe based on a 1H-pyrrol-3(2H)-one scaffold for monitoring H2S levels in biological samples.

Discovery of the biological signaling roles of H2S has spurred great interest in developing reliable methods for its accurate detection and quantification. As considerable variation in its levels is seen during pathological conditions such as sepsis, real-time quantification methods have relevance in diagnosis as well. Of various approaches, reaction-based probes which respond through 'off-on' fluorescence emission remain the most studied. Since the intensity of emission is related to the analyte concentration in these measurements, the presence of built-in features which provide an opportunity for internal referencing will be advantageous. In view of this, a dual mode response system that senses H2S through characteristic fluorescence and Raman (SERS) signals based on a 1H-pyrrol-3(2H)-one scaffold was developed and is the main highlight of this report. This probe offers several advantages such as fast response (<1 min), and high selectivity and sensitivity with a detection limit of ∼7 nM. Imaging of H2S in HepG2 cells, making use of the SERS signal from the thiolysis product is also demonstrated.

Hybridization of the Pharmacophoric Features of Discoipyrrole C and Combretastatin A-4 toward New Anticancer Leads.

Pharmacophore hybridization is an attractive strategy to identify new leads against multifactorial diseases such as cancer. Based on literature analysis of compounds possessing 'vicinal diaryl' fragment in their structure, we considered Discoipyrroles A-D and Combretastatin A-4 (CA-4) as possible components in hybrid design. Discoipyrrole C (Dis C) and CA-4 were used as reference compounds in these studies and their hybrids, in the form of 4,5-diaryl-1H-pyrrol-3(2H)-ones, were synthesized from suitable amino acid precursors though their ynone intermediates. Of these, the hybrid having exact substitution pattern as that of CA-4 showed better potency and selectivity than Dis C, but its activity was less compared to CA-4. This new analog disrupted interphase microtubules by inhibiting tubulin assembly by binding to the colchicine site, induced multipolar spindles, caused cell cycle block and apoptosis in HeLa cells. It also inhibited colony formation and migration of breast cancer cell lines.

Attenuation of tacrolimus induced oxidative stress, mitochondrial damage, and cell cycle arrest by Boerhavia diffusa root fraction in mdck cell lines.

OBJECTIVES: The protective effect of ethyl acetate fraction (EAF) of Boerhavia diffusa roots against Tacrolimus (TAC) induced nephrotoxicity was studied using MDCK cell lines. MATERIALS AND METHODS: Ethanolic root extract of B. diffusa was fractionated using the liquid-liquid partition method. The cytotoxic effect of TAC and protective effect of EAF co-treatment were studied in MDCK cell lines by measuring ROS, LPO, and NO levels; collagen accumulation, effect on mitochondrial membrane integrity and cell cycle analysis were studied. The active component in EAF was quantified by HPLC analysis. RESULTS: TAC induced toxicity, leading to apoptosis and necrosis, was significantly reduced (P<0.001) in EAF co-treatment, with reversal of cell cycle arrest and reduced cell population at sub G0/G1 phase. Further, ROS (P<0.05), LPO and NO (P<0.001), were significantly reduced with EAF co-treatment compared with TAC individually treated cells. TAC induced mitochondrial membrane integrity loss was found to be significantly reduced in co-treated cells, as measured by rhodamine123 (P<0.05) and translocation of cytochrome c (P<0.001) from nucleus to cytoplasm, and caspase 3 release (P<0.001). The same was confirmed through annexin-FITC and PI staining (P<0.05) with reduced apoptotic and necrotic death in co-treated population. Interestingly, EAF co-treatment decreased collagen accumulation (P<0.001) with significant increase in the cell survival of tubular epithelial cells. HPLC analysis showed the presence of Quercetin (87.5 mg/g) in EAF, which may be responsible for the nephroprotective role. CONCLUSION: Thus, these results provide sound evidence that EAF may be an effective adjuvant therapy to prevent nephrotoxicity induced by TAC.

Effective Strategies and Applications of Dendrimers in the Treatment of Ovarian Cancer.

Ovarian cancer, the worldwide leading cause of gynecological cancer-related death, is primarily treated by surgery followed by platinum chemotherapy. Though the tumor initially responds to the treatment, only 30% of 5 year survival period has been recorded and this is mainly attributed to the acquired chemo resistance and frequent recurrence of tumor. Combination chemotherapy as well, led to therapeutic failure due to non-specificity and subsequent side effects. However, polymer mediated drug delivery aids in overcoming these impediments. In particular, three dimensional macromolecule "Dendrimer" with its unique properties and numerous functionalities offer various advantages over the conventional approach and may improve the treatment outcome in patients with ovarian cancer. The present review highlights the various strategies employed using dendrimers to achieve targeted drug delivery and enhanced therapeutic efficacy in ovarian cancer.

Tumor targeting using polyamidoamine dendrimer-cisplatin nanoparticles functionalized with diglycolamic acid and herceptin.

Polymer mediated drug delivery system represents a novel promising platform for tumor-targeting with reduced systemic side effects and improved chemotherapeutical efficacy. In this study, we report the preparation and characterization of herceptin targeted, diglycolamic acid (DGA) functionalized polyamidoamine (PAMAM) dendrimer as a potent drug carrier for cisplatin. DGA dendrimers carrying cisplatin demonstrated enhanced anticancer activity when targeted with herceptin. In vitro cell line studies with herceptin-DGA-G4-cisplatin in HER-2 +ve and HER-2 -ve human ovarian cancer cell lines showed that these nanoparticles possessed remarkable features such as lower IC50 value, improved S-phase arrest, and enhanced apoptosis due to increased cellular uptake and accumulation than the untargeted DGA-G4-cisplatin and free cisplatin. Furthermore, in vivo results in SCID mice bearing SKOV-3 tumor xenografts, herceptin-DGA-G4-cisplatin, appeared to be more effective in inducing tumor regression as compared to free cisplatin. Collectively, these results indicate that herceptin targeted DGA functionalized PAMAM-cisplatin conjugates serve as better anti-tumor agents than individual therapeutic agents.

Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications.

The focus on nanotechnology in cancer treatment and diagnosis has intensified due to the serious side effects caused by anticancer agents as a result of their cytotoxic actions on normal cells. This nonspecific action of chemotherapy has awakened a need for formulations capable of definitive targeting with enhanced tumor-killing. Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important area of nanomedicine. Currently several nanomaterial-based drug-delivery systems are in vogue and several others are in various stages of development. Tumor-targeted drug-delivery systems are envisioned as magic bullets for cancer therapy and several groups are working globally for development of robust systems.