In Vitro Antioxidant and Cytotoxic Analysis of Boerhaavia diffusa Linn.

The present study was carried out to evaluate the antioxidant and cytotoxic activity of unexploited plant, Boerhaavia diffusa indigenous to India. Different concentrations of the ethanolic whole-plant extracts (1000, 500, 250, 125, 50, 25, 12.5 μg/ml) were subjected to 1,1-diphenyl -2-picryl hydrazyl (DPPH) radical scavenging, reducing power activity and cytotoxic study against vero cell lines. The maximum DPPH radical scavenging potential was found to be 93% at 1000 μg/ml with IC50 (Inhibitory Concentration) value being 49.95±1.15 μg/ml. The maximum reducing power of the extract at 700nm was found to be 0.997±0.081 at 1000 μg/ml. The inhibition percentage with regard to cytotoxicity was found to be 89 % at 1000 μg/ml with IC50 value of 50+0.03 μg/ml

Synthesis and Cytotoxic Analysis of Some Disodium 3β,6β-Dihydroxysterol Disulfates

Disodium 3β,6β-dihydroxy-5α-cholestane disulfate (1) was synthesized in 4 steps with a high overall yield from cholesterol. First, cholesterol (4a) was converted to cholest-4-en-3,6-dione (5a) via oxidation with pyridinium chlorochromate (PCC) and then 5a was reduced by NaBH4 in the presence of NiCl2 to produce cholest-3β,6β-diol (6a). The reaction of 6a with the triethylamine-sulfur trioxide complex generated diammonium 3β,6β-dihydroxy-5α-cholestane disulfate (7a) and the treatment of 7a by cation exchange resin 732 (sodium form)(Na+) yielded the target steroid 1. Disodium 24-ethyl-3β,6β-dihydroxycholest-22-ene disulfate (2) and disodium 24-ethyl-3β,6β-dihydroxycholestane disulfate (3) were synthesized using a similar method. The cytotoxicity of these compounds against Sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells was investigated. Our results indicate that presence of a cholesterol-type side chain at position 17 is necessary for their biological activity

Synthesis and Cytotoxic Analysis of Some Disodium 3β,6β-Dihydroxysterol Disulfates

Disodium 3β,6β-dihydroxy-5α-cholestane disulfate (1) was synthesized in 4 steps with a high overall yield from cholesterol. First, cholesterol (4a) was converted to cholest-4-en-3,6-dione (5a) via oxidation with pyridinium chlorochromate (PCC) and then 5a was reduced by NaBH4 in the presence of NiCl2 to produce cholest-3β,6β-diol (6a). The reaction of 6a with the triethylamine-sulfur trioxide complex generated diammonium 3β,6β-dihydroxy-5α-cholestane disulfate (7a) and the treatment of 7a by cation exchange resin 732 (sodium form)(Na+) yielded the target steroid 1. Disodium 24-ethyl-3β,6β-dihydroxycholest-22-ene disulfate (2) and disodium 24-ethyl-3β,6β-dihydroxycholestane disulfate (3) were synthesized using a similar method. The cytotoxicity of these compounds against Sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells was investigated. Our results indicate that presence of a cholesterol-type side chain at position 17 is necessary for their biological activity

Phytochemical and cytotoxic analysis of Pharthenium hysterophosis selected from District Bannu, Pakistan

Parthenium hysterophorus is a well known medicinal plant widely used traditionally in the treatment of various diseases and as a constituent of various drugs, and in phytotherapy. The current study was designed to investigate the phytochemical screening and cytotoxic capacity of methanolic and n-hexane extract of P. hysterophorus. Quantitative analysis of P. hysterophorus showed maximum quantity of flavonoids in methanolic extract of P. hysterophorus which turned down gradually in n-hexane extract of P. hysterophorus due to the decrease in organic solvents polarity. Similar results were also observed for saponins and tannins during this investigation. The highest quantity of alkaloids was recorded in the methanolic extract of P. hysterophorus when compared to n-hexane extract. The extracts also showed maximum cytotoxic potential in various concentrations of n-hexane and methanolic extract of P. hysterophorus. The results revealed that P. hysterophorus contains a remarkable cytotoxic activity due to the presence of bioactive constituents.Key words: Parthenium hysterophorus, cytotoxic, phytochemical screening

Comparative pharmacokinetic and cytotoxic analysis of three different formulations of mitoxantrone in mice.

Two liposomal formulations of mitoxantrone (MTO) were compared with the aqueous solution (free MTO) in terms of their pharmacokinetic behaviour in ICR mice and cytotoxic activity in a nude mouse xenograft model. The three different formulations of MTO [free MTO, phosphatidic acid (PA)-MTO liposomes, pH-MTO liposomes] were administered intravenously (three mice per formulation and time point) at a dose of 4.7 micromol kg(-1) for free MTO, 6.1 micromol kg(-1) for PA-MTO and 4.5 micromol kg(-1) for pH-MTO. The concentrations of MTO were determined using high-performance liquid chromatography (HPLC) in blood, liver, heart, spleen and kidneys of the mice. Additionally, the toxicity and anti-tumour activity of MTO was evaluated in a xenograft model using a human LXFL 529/6 large-cell lung carcinoma. The dose administered was 90% of the maximum tolerated dose (MTD) of the corresponding formulation (8.1 micromol kg(-1) for free MTO, 12.1 micromol kg(-1) for PA-MTO and pH-MTO). The pharmacokinetic behaviour of PA-MTO in blood was faster than that of free MTO, but the cytotoxic effect was improved. In contrast, pH-MTO showed a tenfold increased area under the curve (AUC) in blood compared with free MTO, without improvement of the cytotoxic effect. This discrepancy between the pharmacokinetic and cytotoxic results could be explained by the fact that MTO in pH-MTO liposomes remains mainly in the vascular space, whereas MTO in PA-MTO liposomes is rapidly distributed into deep compartments, even more so than free MTO

Regulation of autoimmunity and donor cell engraftment by recipient Lyt-2+ cells during the graft-versus-host reaction.

When lymphocytes from DBA/2 mice are transferred to (C57BL X DBA/2)F1 (BDF1) mice, the ensuing graft-vs.-host reaction (GVHR) causes an autoimmune illness resembling human SLE. To examine the role of recipient T cells in this process, BDF1 mice were depleted of L3T4+ or Lyt-2+ cells by thymectomy followed by treatment with mAbs to L3T4 or Lyt-2. This produced sustained depletion of these T cell subsets. Subsequent grafting with parental DBA/2 lymphocytes produced autoimmune disease in mice depleted of L3T4+ cells and controls but not in mice depleted of Lyt-2+ cells. Analysis of blood lymphocytes 4 wk after donor cell transfer demonstrated that BDF1 recipients depleted of Lyt-2+ cells were virtually repopulated with donor T lymphocytes, compared with less than or equal to 35% donor cell engraftment in all other groups. Thus, recipient Lyt-2+ cells influence both host cell engraftment and autoimmunity during the parent-into-F1 GVHR

ANALISIS AKTIVITAS ANTIOKSIDAN DAN SITOTOKSIK SENYAWA PELARGONIDIN SEBAGAI KANDIDAT OBAT MENGGUNAKAN METODE DFT (DENSITY FUNCTIONAL THEORY)

 The antioxidant properties of pelargonidin compounds were studied using the DFT/B3LYP/6-31G method in the gas phase and aqueous solvent. Toxicity analysis was studied using the OSIRIS Property Explorer program. Antioxidant measurement parameters such as BDE, IP, PDE, PA, and ETE values of pelargonidin compounds indicate that the suitable reaction mechanism in the process of radical inhibition by pelargonidin compounds is the SET-PT mechanism because it produces the smallest total energy of IP + PDE. The presence of water in the pelargonidin compound increased the BDE, IP, PDE, PA, and ETE values. Cytotoxic analysis showed that pelargonidin compounds are not mutagenic, do not cause irritation, do not cause tumors, and do not cause interference with the reproductive system. Pelargonidin has a drug score of 0.43 which indicates that pelargonidin is a potential drug candidate

ANALISIS AKTIVITAS ANTIOKSIDAN DAN SITOTOKSIK SENYAWA PELARGONIDIN SEBAGAI KANDIDAT OBAT MENGGUNAKAN METODE DFT (DENSITY FUNCTIONAL THEORY)

 The antioxidant properties of pelargonidin compounds were studied using the DFT/B3LYP/6-31G method in the gas phase and aqueous solvent. Toxicity analysis was studied using the OSIRIS Property Explorer program. Antioxidant measurement parameters such as BDE, IP, PDE, PA, and ETE values of pelargonidin compounds indicate that the suitable reaction mechanism in the process of radical inhibition by pelargonidin compounds is the SET-PT mechanism because it produces the smallest total energy of IP + PDE. The presence of water in the pelargonidin compound increased the BDE, IP, PDE, PA, and ETE values. Cytotoxic analysis showed that pelargonidin compounds are not mutagenic, do not cause irritation, do not cause tumors, and do not cause interference with the reproductive system. Pelargonidin has a drug score of 0.43 which indicates that pelargonidin is a potential drug candidate

Analysis of concentration-dependent effects of copper and PCB on different Chattonella spp. microalgae (Raphidophyceae) cultivated in artificial seawater medium

In the present study, the effect on the chlorophyll a and the total protein content as well as the Chattonella spp. cell viability were examined after concentration-dependent exposure to CuCl2 and Aroclor 1242. The comparison between various raphidophyte strains provides an insight into the different susceptibilities to contaminants of Chattonella subsalsa (CSNAV-1), C. marina var . marina (CMCV-1) and C. marina var. ovata (COPV-2). The microalgae were cultivated in artificial seawater medium. Exponentially growing microalgae (8-10 days in culture) were used for exposure experiments. We observed in all three raphidophyte species cytotoxicity-mediated modifications beginning at concentrations of 150 and 200μM of the heavy metal copper after 24 hours exposure. But interestingly, the three strains exhibited only slight differences in their susceptibility to CuCl2. C. subsalsa and C. marina var. marina cells were first affected at the chlorophyll a level and in cell viability. The total protein amount was reduced significantly only after exposure to 300μM of CuCl2. However, C. marina var. ovata microalgae showed similar reduction curves for all three analysed cytotoxicity endpoints after heavy metal exposure. On the other hand, after Aroclor 1242 incubation the cytotoxic modification pattern indicated clearly the different susceptibilities of the three raphidophyte strains. C. subsalsa cells noticeably exhibited a decrease in the analysed pigment amount (30-20% compared to that of the control) already after 0.007mg/L PCB exposure. In contrast, cell viability and total protein content were slightly reduced and fell below the 50% threshold after 0.7 and 3.3mg/L of Aroclor 1242, respectively. Interestingly, C. marina var. ovata showed almost no cytotoxic modification caused by the PCB mixture. Only the concentration of 0.7mg/L Aroclor 1242 clearly affected the cell viability. As opposed to that we observed a concentration-dependent decrease of cell viability and chlorophyll a amount in CMCV-1 microalgae. These observations confirmed that the susceptibility of the raphidophytes strains CSNAV-1, CMCV-1 and COPV-2 is contaminant- dependent. We showed differences even between two variants of Chattonella (Chattonella marina var. marina and C. marina var. ovata). Furthermore, we were able to show the different mode of action of two common pollutants by simple cytotoxic parameters like total protein and chlorophyll a content as well as by cell counting analysis

Design and Synthesis of Novel Tylophorine Analogs and their Biological Activity

Alkaloids containing the nitrogen atom in the bridgehead position of two rings, such as indolizidine, pyrrolizidine, and quinolizidine alkaloids, have a wide and varied distribution in nature. Some of these alkaloids demonstrate a broad range of pharmacological activities and have generated substantial synthetic interest. This thesis covers the total synthesis of novel tylophorine analogs called DCB 3503, DCB 3506, DCB 3507, DCB 3508, DCB 3509, and a derivative with a biotinylated chain attached to DCB 3506 for use as a biological probe. This thesis discusses the biological activity of these compounds as well