Histoprotective effect of rutin against cisplatin-induced toxicities in tumor-bearing mice: Rutin lessens cisplatin-induced toxicities.

Cisplatin is an effective anticancer drug used against a variety of cancers. The full therapeutic potential of cisplatin is often hampered due to concurrent development of various side effects in the hosts. Rutin, a naturally occurring bioflavonoid shows several pharmacological activities. It has been earlier reported by us that rutin and cisplatin in combination show better antitumor activity against murine ascites Dalton's lymphoma. As cisplatin is given to cancer-bearing hosts only, the present study was undertaken to explore the histoprotective effect of rutin against some toxicities induced by cisplatin in tumor-bearing mice. Cisplatin treatment caused severe damages in tissue architecture such as degenerated hepatocytes with nuclear condensation and sinusoidal dilatation in the liver, glomerular deterioration, infiltration of cells, and tubular congestion in the kidney, and vacuolization of Sertoli cells or dense granules in the cytoplasm and damaged seminiferous tubules in the testes. In the rutin plus cisplatin combination-treated mice, all the abnormal tissue architectural features were decreased. Further, as compared to cisplatin treatment, combination treatment did not show any significant elevation in the liver functional biomarkers (serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase) and renal functional biomarkers (serum urea and creatinine levels). The combination treatment reduced the sperm abnormalities also as compared to the cisplatin alone treatment. The in vitro hemolysis assay of red blood cells and scanning electron microscopy revealed that combination treatment lessened the cisplatin-induced hemolysis and abnormalities in RBCs. Thus, the present findings demonstrate that rutin has histoprotective ability against cisplatin-induced toxicities in tumor-bearing mice.

Instability of Rotationally Tuned Dipolar Bose-Einstein Condensates.

The possibility of effectively inverting the sign of the dipole-dipole interaction, by fast rotation of the dipole polarization, is examined within a harmonically trapped dipolar Bose-Einstein condensate. Our analysis is based on the stationary states in the Thomas-Fermi limit, in the corotating frame, as well as direct numerical simulations in the Thomas-Fermi regime, explicitly accounting for the rotating polarization. The condensate is found to be inherently unstable due to the dynamical instability of collective modes. This ultimately prevents the realization of robust and long-lived rotationally tuned states. Our findings have major implications for experimentally accessing this regime.

Crystal structure of 1'-ethyl-spiro[chroman-4,4'-imidazolidine]-2',5'-dione: a hydantoine derivative.

The title compound, C13H13N2O3, a hydantoin derivative, crystallized with two mol-ecules (A and B) in an asymmetric unit. In mol-ecule A, the imidazolidine ring is twisted about the C-N bond involving the spiro C atom, while in mol-ecule B this ring is flat (r.m.s. deviation = 0.010 Å). The pyran rings in both mol-ecules have distorted half-chair conformations. The mean plane of the imidazolidine ring is inclined to the aromatic ring of the chroman unit by 79.71 (11)° in mol-ecule A and 82.83 (12)° in mol-ecule B. In the crystal, pairs of N-H⋯O hydrogen bonds link the individual mol-ecules to form A-A and B-B inversion dimers. The dimers are linked via N-H⋯O and C-H⋯O hydrogen bonds, forming sheets lying parallel to the bc plane, viz. (011). Within the sheets, the A and B mol-ecules are linked by C-H⋯π inter-actions.

Crystal structure of ethyl 2-(3,5-di-fluoro-phen-yl)quinoline-4-carboxyl-ate.

In the title compound, C18H13F2NO2, the two rings of the quinoline system are fused almost coaxially, with a dihedral angle between their planes of 2.28 (8)°. The plane of the attached benzene ring is inclined to the plane of the quinoline system by 7.65 (7)°. The carboxyl-ate group attached to the quinoline system is in an anti-periplanar conformation. There is a short intra-molecular C-H⋯O contact involving the carbonyl group. In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds, forming chains lying in the (1-10) plane.

Crystal structure of 1'-(2-methyl-prop-yl)-2,3-di-hydro-spiro-[1-benzo-thio-pyran-4,4'-imidazolidine]-2',5'-dione.

In the title compound, C15H18N2O2S, the 2,3-di-hydro-1-benzo-thio-pyran ring adopts a sofa conformation and the hydantoin ring is twisted with respect to the benzene ring at 78.73 (17)°. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into inversion dimers.

Crystal structure of 1-ethyl-spiro-[imid-az-olidine-4,1'-indane]-2,5-dione.

In the title compound, C13H14N2O2, the C5 ring has an envelope conformation with the C atom adjacent to the quaternary C being the flap. The five atoms comprising the imidazolidine-2,4-dione ring are almost planar (r.m.s. deviation = 0.004 Å). The dihedral angle between the five-membered rings is 89.66 (10)°. In the crystal, inversion-related mol-ecules are connected via {⋯HNCO}2 synthons. These are linked into a helical supra-molecular chain along [010] by C-H⋯O inter-actions.

Human semen study around and away from gold mine area.

Gold was first detected in human semen in 1981. The entry of gold into semen was hypothesized through food items. Earlier reports identified gold in semen as important for good quality of semen. The infertility rate could be low around gold mine area when compared to other places. The aim of the study was to verify this. Towards this, the quality of human semen around a gold mine (Kolar, India) was evaluated and compared to that from a place which was 2000 km away from a gold mine (Jamnagar, India). A total number of 254 semen samples from Kolar and 437 from Jamnagar were evaluated. The fertility rate was higher in Kolar region. The semen samples studied for both places showed that the semen quality was superior in Kolar gold field area.

Evaluation of in vivo wound-healing potential of 2-[4-(2,4-dimethoxy-benzoyl)-phenoxy]-1-[4-(3-piperidin-4-yl-propyl)-piperidin-1-yl]-ethanone derivatives.

Series of 2-[4-(2,4-dimethoxy-benzoyl)-phenoxy]-1-[4-(3-piperidin-4-yl-propyl)-piperidin-1-yl]-ethanone derivatives 9(a-d) and 10(a-d) were synthesized in good yield. The synthesized compounds were characterized by (1)H NMR, LC-MS, FTIR and elemental analysis. All the compounds were screened for in vivo wound-healing activity by incision and dead space wound models on Swiss albino rats. Significant wound healing was observed in 10b and 10d treated groups as also the epithelialization of the incision wound was faster with a high rate of wound contraction in these groups. The tensile strength of the incision wound was significantly increased in 10b and 10d compared to the Nitrofurazone, the standard skin ointment. In dead space wound model also the weight of the granulation was higher indicating increase in collagenation. The SAR correlation studies revealed that the thioamide functional linkage and electron withdrawing groups influence the wound-healing activity.

Synthesis and antimicrobial activity of 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl) propyl)piperidine derivatives against pathogens of Lycopersicon esculentum: a structure-activity evaluation study.

Several 1-benzhydryl-sulfonyl-4-(3-(piperidin-4-yl)propyl)piperidine derivatives 8(a-j) were prepared by the treatment of substituted benzhydryl chlorides with 4-(3-(piperidin-4-yl)propyl)piperidine followed by N-sulfonation with sulfonyl chlorides in the presence of dry methylene dichloride and triethyl amine. The synthesized compounds were characterized by (1)H-NMR, IR, and elemental analysis. All the synthesized compounds were evaluated in vitro for their efficacy as antimicrobial agents by artificial inoculation technique against standard strains of two important bacterial viz., Xanthomonas axonopodis pv. vesicatoria and Ralstonia solanacearum as well as and two fungal pathogens namely Alternaria solani and Fusarium solani of tomato plants. We have briefly investigated the structure-activity relation studies and reveal that the nature of substitutions on benzhydryl ring and sulfonamide ring influences the antibacterial activity. Among the synthesized new compounds 8b, 8d, 8g, 8h, 8i, and 8j were showed significant potent antimicrobial activities compared to the standard drugs chloramphenicol, mancozeb.

Synthesis and in vitro antiproliferative activity of novel 1-benzhydrylpiperazine derivatives against human cancer cell lines.

In order to explore the antiproliferative effect associated with the piperazine framework, several 1-benzhydrylpiperazine derivatives 8(a-d), 9(a-d) and 10(a-h) were synthesized. Variation in the functional group at N-terminal of the piperazine led to three sets of compounds, bearing the sulfonyl, amide and thiourea, respectively. Their chemical structures were confirmed by (1)H NMR, LCMS, IR and elemental analysis. The antiproliferative effect of the compounds were evaluated in vitro using the MTT colorimetric method against one normal cell line (NF-103 skin fibroblast cells) and four human cancer cell lines (MCF-7 breast carcinoma cell line, HepG-2 hepatocellular carcinoma cell line, HeLa cervix carcinoma cell line and HT-29 colon carcinoma cell line) for the time period of 24 h. Among the series, four compounds exhibited interesting growth inhibitory effects against all four cell lines.

Synthesis and in vitro cytotoxic evaluation of novel diazaspiro bicyclo hydantoin derivatives in human leukemia cells: a SAR study.

To study the structure activity relationship (SAR) on the cytotoxic activity and probe the structural requirement for the potent antitumor activity, a series of novel diazaspiro bicyclo hydantoin derivatives were designed and synthesized. Their structures were confirmed by (1)H NMR, LCMS and IR analyses. The antiproliferative effect of these compounds were determined against human leukemia, K562 (chronic myelogenous leukemia) and CEM (T-cell leukemia) cells using trypan blue and MTT assay, and the SAR associated with the position of N-terminal substituents in diazaspiro bicyclo hydantoin have also been discussed. It has been observed that these compounds displayed strong, moderate and weak cytotoxic activities. Interestingly, compounds having electron withdrawing groups at third and fourth position of the phenyl ring displayed selectively cytotoxic activities to both the cell lines tested with IC(50) value lower than 50 muM. In addition, the cytotoxic activities of the compounds 7(a-o) bearing the substituents at N-3 position of diazaspiro bicyclo hydantoin increases in the order alkene > ester > ether and plays an important role in determining their antitumor activities. The position and number of substituents in benzyl group attached to N-8 of diazaspiro bicyclo hydantoin nucleus interacted selectively with specific targets leading to the difference of biochemical and pharmacological effects.

Synthesis and antiproliferative activity of substituted diazaspiro hydantoins: a structure-activity relationship study.

In the course of structure-activity relationship studies and to explore the antiproliferative effect associated with the hydantoin framework, diversely substituted several diazaspiro hydantoins were synthesized. Variation in the functional group at N-terminal of the hydantoin ring and coupling of different substituted aromatic acids in 4-aminocyclohexanone ring led to three sets of compounds. The antiproliferative effect of the compounds was evaluated in vitro using the MTT colorimetric method against one normal cell line (NDF-103 skin fibroblast cells) and four human cancer cell lines (MCF-7 breast carcinoma cell line, HepG-2 hepatocellular carcinoma cell line, HeLa cervix carcinoma cell line and HT-29 colon carcinoma cell line) for the time period of 24 h. Among the series, some compounds exhibited interesting growth inhibitory effects against all four cell lines. From the SAR studies, it reveals that, the substitution at N-terminal in hydantoin ring plays key role in the antiproliferative activity.

Synthesis of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives as antiproliferative agents: a structure-activity relationship study.

A series of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives 5(a-m) were synthesized with different substituted aromatic/heterocyclic acid chlorides (R-CO-Cl) and characterized by (1)H NMR, LC/MS, FTIR and elemental analyses. All the compounds synthesised were evaluated for their antiproliferative activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antiproliferative effects of the synthesised compounds were tested against viable human skin fibroblast cells and carcinoma cells namely HeLa cells, HT-29 cells, MCF-7 cells, HepG-2 cells by adopting positive and negative control. The importance of the aromatic and heterocyclic moiety was confirmed. From the SAR studies, it reveals that, the substitution at N-terminal of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole by the heterocyclic ring plays a dominant role and was responsible for the antiproliferative activity. Among the synthesized compounds 5a, 5d and 5k have showed potent antiproliferative activity on all the carcinoma cells tested.

Synthesis and evaluation of 1-benzhydryl-sulfonyl-piperazine derivatives as inhibitors of tumor growth and tumor angiogenesis of mouse ehrlich ascites tumor in vivo.

A series of novel 1-benzhydryl-sulfonyl-piperazine derivatives 3(a-e) were synthesized by nucleophilic substitution reaction of 1-benzhydryl-piperazine with different sulfonyl chlorides and were characterized by 1H NMR, LC/MS, FTIR and elemental analysis. In the present study, the compounds 3(a-e) exhibited in vivo inhibition of Ehrlich ascites tumor (EAT) cell growth and increased the Median Survival Time (MST) and %ILS of EAT bearing mice. Further treatment of derivatives in vivo resulted in reduction of EAT cell number and ascites formation. The efficacy of the derivatives to inhibit the angiogenesis in vivo was evaluated in tumor bearing mice peritoneum and chorio allantoic membrane (CAM) model. The compounds suppressed the blood vessel formation in vivo in mice peritoneum and in CAM. Among the compounds studied, 3e demonstrated highest tumor inhibitory and anti-angiogenic effects against mouse tumor. However, this phenomenon needs detailed investigation.

Synthesis and antimicrobial studies of novel 1-benzhydryl-piperazine sulfonamide and carboxamide derivatives.

A series of novel substituted 1-benzhydryl-piperazine sulfonamide 8(a-f) and benzamides 9(a-h) were synthesized and their antimicrobial activities evaluated in vitro by paper disc diffusion and micro dilution method against standard strains of Gram-positive (Staphylococcus aureus ATCC 25953, Staphylococcus epidermis 25212, Bacillus cereus 11778, Bacillus substilis 6051) and Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 2853, Proteus vulgaris ATCC 2853 and Salmonella typhi ATCC 9484) bacteria. Among the synthesized new compounds 8d, 8e, 9c, 9e, 9f and 9 h showed potent antimicrobial activities compared to the standard drug streptomycin.

Synthesis and in vitro antiproliferative activity against human cancer cell lines of novel 5-(4-methyl-benzylidene)-thiazolidine-2,4-diones.

A series of novel 5-(4-methyl-benzylidene)-thiazolidine-2,4-dione derivatives 6 (a-d) and 7 (a-g) were synthesized with different substituted aromatic sulfonyl chlorides (R-SO(2)-Cl) and alkyl halides (R-X) and were characterized by (1)H NMR, LC/MS, FTIR and elemental analyses. All the compounds synthesised were evaluated for their cell antiproliferation activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antiproliferative effects of the synthesised compounds were tested against viable human skin fibroblast cell line and carcinoma cell lines namely HeLa cells, HT-29 cells, MCF-7 cells, HepG-2 cells by adopting positive and negative control. The importance of the nitro group on thiazolidinone moiety was confirmed and it was concluded that the fourth position of the substituted aryl ring plays a dominant role and was responsible for the antiproliferative activity. Among the synthesized compounds only 6a, 7e and 7g have potent antiproliferative activity on all the carcinoma cell lines tested.

Effect of novel N-aryl sulfonamide substituted 3-morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer's dementia models.

A series of novel, potent, and selective muscarinic receptor 1 agonists (M1 receptor agonists) that employ a key N-substituted morpholine Arecoline moiety has been synthesized as part of research effort for the therapy of Alzheimer's diseases. The ester group of arecoline (which is reported as muscarinic agonist) has been replaced by N-substituted morpholine ring. The structure-activity relationship reveals that the electron donating 4-substituted sulfonyl derivatives (9a, 9b, 9c, and 9e) on the nitrogen atom of the morpholine ring increases the affinity of M1 receptor binding 50- to 80-fold greater than the corresponding arecoline. Other derivatives also showed considerable M1 receptor binding affinity.

Synthesis of Novel 3-Aryl-N-Methyl-1,2,5,6-Tetrahydropyridine Derivatives by Suzuki coupling: As Acetyl Cholinesterase Inhibitors.

Alzheimer's disease (AD) is a neurodegenerative disorder affecting the central nervous system, which is also associated with progressive loss of memory and cognition. The development of numerous structural classes of compounds with different pharmacological profile could be an evolving, promising therapeutic approach for the treatment of AD. Thus, providing a symptomatic treatment for this disease are cholinomimetics with the pharmacological profile of Acetylcholinesterase (AChE) inhibitors. In view of this, we have synthesized novel 3-aryl-N-methyl-1,2,5,6-tetrahydropyridine derivatives 5a-k by Suzuki coupling and screened the efficacy of these derivatives for their AChE inhibitor activity.

Antitumour activity of some plants from Meghalaya and Mizoram against murine ascites Dalton's lymphoma.

Total five plants, three from Mizoram (Dillenia pentagyna, Ageratum conyzoides, Blumea lanceolaria) and two from Meghalaya (Potentilla fulgens, Taxus baccata) were studied for their antitumour activity against murine ascites Dalton's lymphoma (DL) in vivo. Only three plants showed the different magnitude of antitumour activity. Out of these three plants, the antitumour activity was maximally observed with the methanol extract of the stem bark of D. pentagyna as compared to the aqueous extract of the roots of A. conyzoides and aqueous extract of the root of P. fulgens. An increase in glutathione levels in Dalton's lymphoma cells was observed during tumour growth. Changes in glutathione and protein levels were also investigated in the liver and Dalton's lymphoma cells of tumour-bearing mice following the treatment with the extract of D. pentagyna which showed the highest antitumour activity as compared to the other two plant extracts. Glutathione in the liver and DL cells of treated tumour-bearing mice was found to be decreased. The protein concentration in liver and DL cells decreased mainly at 96 hr of treatment. It may be concluded that the natural product of D. pentagyna promises to be more active against Dalton's lymphoma than others and the decrease in glutathione level may be one of the important steps in resulting this antitumour effect.

Changes in endogenous tissue glutathione level in relation to murine ascites tumor growth and the anticancer activity of cisplatin.

Changes in glutathione levels were determined in tissues of 11- to 12-week-old Swiss albino mice at different stages of Dalton's lymphoma tumor growth and following cisplatin (8 mg/kg body weight, ip) treatment for 24-96 h, keeping 4-5 animals in each experimental group. Glutathione levels increased in spleen of tumor-bearing compared to normal mice (9.95 +/- 0.14 vs 7.86 +/- 1.64 micromol/g wet weight, P