Synthesis of 1,6-Disubstituted 4,5,6,7-Tetrahydropyrazolo[3,4-c]pyridin-7-one Derivatives and Evaluation of Their Anticancer Activity

Devegowda, Vani Nelamane,Seo, Seon-Hee,Pae, Ae Nim,Nam, Ghil-Soo,Choi, Kyung-Il Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.2

Promising anticancer compounds of the type 1,6-disubstituted 4,5,6,7-tetrahydropyrazolo[3,4-c]pyridin-7-ones were identified. The target compounds were readily synthesized in a large scale via a sequence of reactions starting from the commercially available primary amines. Their in vitro anti-proliferative activity has been evaluated on prostate (DU-145), colon (HT-29 and HCT-116) and melanoma (A375P) human cancer cell lines. The relationships between the structure and the anticancer activity, covering all tested cancer cell lines, revealed that the compound 5c with 2,4-dimethylphenyl substituent at $R^2$ was the most potent with the $IC_{50}$ values in the range as low as 0.16 to $0.40{\mu}M$.

Synthesis of 1,6-Disubstituted 4,5,6,7-Tetrahydropyrazolo[3,4-c]pyridin-7-one Derivatives and Evaluation of Their Anticancer Activity

Vani Nelamane Devegowda,Seon Hee Seo,배애님,Ghilsoo Nam,최경일 대한화학회 2012 Bulletin of the Korean Chemical Society Vol.33 No.2

Promising anticancer compounds of the type 1,6-disubstituted 4,5,6,7-tetrahydropyrazolo[3,4-c]pyridin-7-ones were identified. The target compounds were readily synthesized in a large scale via a sequence of reactions starting from the commercially available primary amines. Their in vitro anti-proliferative activity has been evaluated on prostate (DU-145), colon (HT-29 and HCT-116) and melanoma (A375P) human cancer cell lines. The relationships between the structure and the anticancer activity, covering all tested cancer cell lines,revealed that the compound 5c with 2,4-dimethylphenyl substituent at R2 was the most potent with the IC50values in the range as low as 0.16 to 0.40 μM.

Ability of Modified Glucomannan to Sequestrate T-2 Toxin in the Gastrointestinal Tract of Chicken

Reddy, N.B.,Devegowda, G.,Shashidhara, R.G. Asian Australasian Association of Animal Productio 2004 Animal Bioscience Vol.17 No.2

The ability of Modified Glucomannan (MG) to bind T-2 toxin (T-2) in the gastrointestinal tract has been tested in vivo by feeding 120 five-wk-old broiler chicken with the following six treatment diets, 1) Control diet; 2) Control+MG (0.1%); 3) Control+T-2 (500 ppb); 4) Control+T-2 (500 ppb)+MG (0.1%); 5) Control+T-2 (1,000 ppb) and 6) Control+T-2 (1,000 ppb)+MG (0.1%). Twenty birds were assigned to each treatment group, which had five experimental groups. Four birds of each experimental group were sacrificed at an interval of 30 min i.e. at 0, 30, 60, 90 and 120 min after feeding experimental diets. The whole gut contents of each bird were collected, dried and toxin concentration was determined. Percent T-2 recovered from the gut was significantly lower (p<0.05) in the groups fed MG at all the time intervals. The percent T-2 adsorbed by the MG at different T-2 levels (500 and 1,000 ppb) was 15.97 and 14.77, 22.53 and 22.67, 26.88 and 28.03, and 31.50 and 31.83 at 30, 60, 90 and 120 min, respectively.

Efficacy of Glucomannan-containing Yeast Product (Mycosorb^®) and Hydrated Sodium Calcium Aluminosilicate in Preventing the Individual and Combined Toxicity of Aflatoxin and T-2 Toxin in Commercial Broilers

Girish, C.K.,Devegowda, G. Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.6

A feeding trial was conducted on commercial broilers for a period of 35 days to determine the individual and combined effects of aflatoxin (AF) and T-2 toxin (T-2) on performance, organ weights and immune status. The efficacy of dietary glucomannan-containing yeast product (GYP) ($Mycosorb^{(R)}$) and hydrated sodium calcium aluminosilicate (HSCAS) in preventing the adverse effects of aflatoxin and T-2 toxin was also evaluated. Twelve dietary treatments ($4{\times}3$ factorial) comprising two dietary levels each of AF (0 and 2 mg/kg), T-2 toxin (0 and 1 mg/kg), GYP (0 and 1 kg/ton) and HSCAS (0 and 10 kg/ton) were tested on 720 commercial broiler chickens divided at random into 36 replicates of 20 chicks each (10 males and 10 females). Weight gain and feed intake were recorded weekly. Organ morphology and antibody titers for Newcastle disease (ND) and infectious bursal disease (IBD) were measured on the $35^{th}$ day. AF and T-2 toxin individually decreased weight gain and increased feed conversion ratio (FCR) (p<0.05). AF alone (p<0.05) increased weights of liver, kidney, gizzard and spleen and reduced thymus and bursal weights. T-2 toxin (p<0.05) increased liver and gizzard weights and decreased thymus weight. Both AF and T-2 toxin when fed individually affected ND and IBD titers in a significant manner. Significant interactions between AF and T-2 toxin were observed for their additive effects on weight gain, FCR, organ weights and antibody titers. Addition of GYP (p<0.05) improved weight gain, feed conversion efficiency and restored the organ weights. Antibody titers against ND and IBD were significantly improved with the supplementation of GYP. Supplementation of HSCAS (p<0.05) resulted in improvement in weight gain and restored organ weights in the groups fed AF alone, but not in T-2 toxin fed groups. HSCAS inclusion did not influence FCR in toxin fed groups. Addition of HSCAS (p<0.05) improved the antibody titers against ND and IBD only in AF fed groups. Thus, the results indicate that addition of GYP is effective in averting the individual and combined toxicity of aflatoxin and T-2 toxin in commercial broilers, while HSCAS is effective only against aflatoxin.

Effects of Enzyme Addition to Broiler Diets Containing Varying Levels of Double Zero Rapeseed Meal

Ramesh, K.R.,Devegowda, G.,Khosravinia, H. Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.9

Maize-soybean meal diets with 0, 100, 200 and 300 g/kg double zero rapeseed meal ('00' RSM) with and without an enzyme mixture (xylanase, pectinase, cellulase) at a level of 1.6 g/kg were evaluated with 624 day-old broiler chicks for 5 weeks. The birds were randomly allocated to eight dietary treatments with three replicates of 26 birds each. Average daily gain (ADG) and feed intake (FI) were recorded weekly and ileal viscosity, organ weights, serum enzyme activity, hormonal profile and hematological parameters were measured at the end of week 5. Average daily gain during the weekly periods was significantly influenced by the dietary level of '00'RSM (p<0.01). Inclusion of '00' RSM improved the ADG up to day 28 with the increased level; beyond that time no improvement was recorded when compared to control groups. However, ADG from 1-35 days was significantly different between 300 g/kg inclusion level of '00' RSM and the control diet. Inconsistent decline in feed intake and feed conversion ratio was observed up to day 21 and the trend was reversed thereafter. The proportion of '00' RSM in the diet had a significant ($p{\leq}0.05$) influence on thyroid weight but had no effect on the relative weights of liver and heart, serum enzyme activities (${\gamma}$-glutamyl transferase, alanine amino transferase and aspartate amino transferase), thyroid hormones ($T_3$ and $T_4$), hemoglobin level and hematocrit. Significant improvement in ADG was recorded during the 2nd week of age with the addition of enzyme, whereas for all other periods, including the whole period of the trial, higher but non-significant ADG was observed. FI and FCR were not affected by the addition of enzyme but there was a numerical reduction in FCR during the whole period. The addition of enzyme reduced the ileal viscosity at all levels of '00' RSM inclusion. The results suggest that '00' RSM can be included up to 300 g/kg in broiler diets without any adverse effects on health and performance. The addition of commercial enzyme mixture containing xylanase, pectinase, cellulase to broiler diets containing '00'RSM has some effect on growth rate and feed conversion efficiency.

Esterified-Glucomannan in Broiler Chicken Diets-Contaminated with Aflatoxin, Ochratoxin and T-2 Toxin: Evaluation of its Binding Ability (in vitro) and Efficacy as Immunomodulator

Raju, M.V.L.N.,Devegowda, G. Asian Australasian Association of Animal Productio 2002 Animal Bioscience Vol.15 No.7

In vitro binding efficacy of esterified glucomannan (E-GM) (0.1%) on aflatoxin B1 (AF) (300 ppb), ochratoxin A (OA) (2 ppm) and T-2 toxin (T-2) (3 ppm), when present alone or in combination, was evaluated in toxin-contaminated feed at pH 4.5 and 6.5. Esterified glucomannan showed significantly (p<0.01) higher binding with AF (81.6%), whereas those recorded with T-2 (27.8%) and OA (25.6%) were moderate. Binding of each toxin decreased as the number of toxins in feed increased. pH of medium showed no effect on mycotoxin binding ability of E-GM. A $2{\times}2{\times}2{\times}2$ factorial experiment of 5 week duration was conducted to study the effects of two dietary levels each of AF (0 and 300 ppb), OA (0 and 2 ppm), T-2 (0 and 3 ppm ) and E-GM (0 and 0.1%) on the immune competence of a total of 960 day-old commercial broilers. Reductions in size of thymus (by AF and T-2) and bursa (by AF) and antibody titers against Newcastle disease and Infectious Bursal disease (by all the toxins) were noted. Additive and antagonistic interactions were seen among the toxins on certain parameters. Esterified glucomannan significantly (p<0.01) improved antibody titers and weights of bursa ofFabricius and thymus indicating its counteracting efficacy against immunosuppression in mycotoxicosis of multiple origin.