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1.
MethodsX ; 4: 128-133, 2017.
Article in English | MEDLINE | ID: mdl-28289606

ABSTRACT

The study was undertaken to develop a simplified procedure for the isolation of bioactive isoflavone from Iris kashmiriana, using a direct method of isolation, avoiding the use of chromatographic techniques. The compound was isolated by commercially viable procedure. The extraction of powdered drug (500 g) was done with petroleum ether (60-80) using a Soxhlet apparatus (24 h run). The petroleum ether extract (gums and resins 2.13 g) was obtained and the marc (400 g) was subjected to extraction with 95% methanol using a Soxhlet apparatus (24 h run). The methanolic extract (5 g) was subjected to successive fractionation with toluene, chloroform and ethyl acetate and n- butanol. On the basis of phytochemical analysis, the glycoside was present in n- butanol fraction. The n-butanol fraction (1.5 g) was taken in dried methanol, passed through activated animal charcoal and subjected to acid hydrolysis. The isoflavone (250 mg), was obtained after the usual process of separation. The purity of the compound was checked by analyzing TLC (Thin Layer chromatography) and melting point. Further, the chemical method was used to characterize the compound by shift reagents using UV spectroscopy. The quantitative estimation of isoflavone was done using RP-HPLC and was found to be 98.9% pure. •The "previously undescribed" isoflavone was isolated by modifying approach of solvent/solvent extraction, fractionation and acid hydrolysis.•The spectroscopic characterization was equaly done by IR, 1HNMR, 13CNMR, Mass spectrometry.•98.9% purity was achieved using RP-HPLC with simple solvent (Methanol and Water 55: 45).

2.
Phytochemistry ; 136: 70-80, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28108024

ABSTRACT

Cancer is possibly one of the most devastating and complex disease and therefore involves chemotherapy as one of the frontline strategies in its therapy. However, expected toxicity and resistance with chemotherapeutic agents encourage us to use the plant derived natural chemotherapeutic sources at the clinical stage of cancer therapy. In view of this strategy, herein new glycosides and isoflavonoids were isolated from Iris kashmiriana Baker and subjected to structure elucidation followed by their biological evaluation. Isolated compounds and their derivatives were purified by the column chromatography and structural identification was made by a combination of various spectroscopic technique vis. UV, IR, 1H NMR, 13C NMR, DEPT, 2-D NMR and mass spectrometry coupled with chemical analysis. Furthermore, an in silico library of isolated isoflavones and its analogues were designed. NF-kappaB (transcription factor that facilitates angiogenesis, inflammation, invasion and metastasis) was selected as a target to evaluate the anticancer and antioxidant activity of isoflavones and its analogues. Designed library of isoflavones and analogues were docked into the active site of NF-kappa B and the most active 15 analogues were selected for synthesis. Finally, all compounds were evaluated for their cytotoxicity against various cell lines and antioxidant activity with different methods that demonstrate their anti-cancer and anti-oxidant potential. The cell cycle specificity of the cytotoxicity was further analyzed by corresponding analysis, using flow cytometer. Most of the compounds exhibit moderate activity, whereas the 5,7,8-trihydroxy-3-(4-methoxyphenyl)-4H-chromen-4-one, 5,7,8-trihydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one, 5,7,8-triacetoxyoxy-3-(4-methoxyphenyl)-4H-chromen-4-one and 6,7-diacetoxyoxy-3-(4-methoxyphenyl)-4H-chromen-4-one showed distinct broad-spectrum anticancer activity with IC50 values ranges between 3.8 and 5.6 µg/mL. Cell cycle analysis indicates that these compounds induced cell cycle arrest at G2/M phase.


Subject(s)
Anti-Anxiety Agents/isolation & purification , Anti-Anxiety Agents/pharmacology , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Cell Cycle Checkpoints/drug effects , Iris Plant/chemistry , Isoflavones/isolation & purification , Isoflavones/pharmacology , NF-kappa B/drug effects , Anti-Anxiety Agents/chemistry , Antineoplastic Agents/chemistry , Cell Survival/drug effects , Glycosides/pharmacology , Humans , Isoflavones/chemistry , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular
3.
Drug Deliv ; 23(1): 55-62, 2016.
Article in English | MEDLINE | ID: mdl-24758141

ABSTRACT

OBJECTIVE: This investigation deals with the development and evaluation (in vitro and in vivo) of pH triggered Eudragit-coated chitosan microspheres of curcumin (CUR) for treating ulcerative colitis. METHODS: CUR-loaded chitosan microspheres were initially prepared by emulsion cross linking method followed by coating with Eudragit S-100. The pharmacodynamics of the developed formulation was analyzed in mice by acetic acid induced colitis model. RESULTS: The developed microspheres were of uniform spherical shape with high entrapment efficiency. CUR-chitosan microspheres showed less intense peaks compared to free CUR confirming inclusion of drug within microspheres as revealed by X-ray diffractogram. Uncoated CUR-chitosan microspheres exhibited burst release within initial 4 h while microspheres coated with Eudragit S-100 prevented premature release of CUR and showed controlled release up to 12 h following Higuchi model. In vivo organ biodistribution study showed negligible amount of CUR in stomach and small intestine confirming integrity of microsphere in upper gastrointestinal tract (GIT). In vivo study revealed significant reduction in severity and extent of colonic damage with CUR-loaded microspheres as compared to pure CUR which was further confirmed by histopathological study. CONCLUSION: In vitro and in vivo studies proved the developed formulations as a promising system for pH-dependent delivery of drug to colon in ulcerative colitis.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Curcumin/administration & dosage , Curcumin/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Acetic Acid , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Chemistry, Pharmaceutical , Chitosan , Cross-Linking Reagents , Curcumin/pharmacokinetics , Drug Delivery Systems , Excipients , Hydrogen-Ion Concentration , Inflammatory Bowel Diseases/chemically induced , Mice , Microspheres , Polymethacrylic Acids , Tissue Distribution
4.
Pharm Dev Technol ; 21(5): 630-5, 2016 Aug.
Article in English | MEDLINE | ID: mdl-25923136

ABSTRACT

OBJECTIVE: The aim of present investigation was to prepare Curcumin-Zn(II) complex in a view to enhance solubility, stability and pharmacodynamic effect in experimentally induced ulcerative colitis. METHOD: Curcumin-Zn(II) complex was prepared by stirring curcumin with anhydrous zinc chloride at a molar ratio of 1:1. The prepared curcumin metallocomplex was characterized by TLC, FTIR, UV spectroscopy and (1)H NMR. In vitro kinetic degradation and solubility of Curcumin and Curcumin-Zn(II) complex was analyzed spectrophotometrically. Pharmacodynamic evaluation of curcumin and its metal complex was assessed in ulcerative colitis in mice. RESULTS: Curcumin showed chelation with zinc ion as confirmed by the TLC, FTIR, UV spectroscopy and (1)H NMR. The results of TLC [Rf value], IR Spectroscopy [shifting of stretching vibrations of υ(C=C) and υ(C=O)], UV spectra [deconvoluted with absorption band at 432-466.4 nm] of Curcumin-Zn(II) complex compared to curcumin confirmed the formation of metallocomplex. (1)HNMR spectra of Curcumin-Zn(II) showed the upfield shift of Ha and Hb. Kinetic stability studies showed metallocomplex with zinc exhibited good stability. In vivo study revealed significant reduction in severity and extent of colonic damage with Curcumin-Zn(II) which were further confirmed by histopathological study. CONCLUSION: This study recognizes higher solubility and stability of Curcumin-Zn(II) complex and suggested better pharmacodynamic effects.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Curcumin/pharmacokinetics , Drug Delivery Systems/methods , Zinc/pharmacokinetics , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/pathology , Curcumin/administration & dosage , Curcumin/chemistry , Drug Stability , Mice , Solubility/drug effects , Zinc/administration & dosage , Zinc/chemistry
5.
Biomed Res Int ; 2014: 340701, 2014.
Article in English | MEDLINE | ID: mdl-25093165

ABSTRACT

The present study was aimed to develop and optimize the microsponges of curcumin for colon specific drug delivery in a view to bypass the upper gastrointestinal tract (GIT) for enhanced therapeutic effect. Microsponges were developed by quasi emulsion solvent diffusion method using 3(2) full factorial design. Prepared microsponges were optimized in order to analyze the effects of independent variables (volume of ethanol and Eudragit L100) on the encapsulation efficiency, particle size, and drug release. The optimized formulation was subjected to in vivo study using acetic acid induced colitis model in rats. The F7 was selected as optimized formulation based on particle size of 41.63 µm, % entrapment efficiency of 78.13%, and % cumulative drug release of 84.12%, and desirability factor of 0.83. Release studies revealed that microsponges prevented the premature release of curcumin in upper GIT and specifically released the drug at colonic pH. The drug release profile of F7 formulation was subjected to different kinetic models and based upon the best correlation coefficient (r(2) = 0.9927) the release was found to follow Higuchi model, which suggested diffusion as the main mechanism of drug release. Pharmacodynamic study showed that curcumin loaded microsponges causes a significant decrease in edema, necrosis, and hemorrhage of colon as compared to free curcumin. This study proves that curcumin loaded microsponges may act as a promising drug delivery system for treatment of ulcerative colitis.


Subject(s)
Colon/drug effects , Curcumin/administration & dosage , Drug Delivery Systems , Inflammatory Bowel Diseases/drug therapy , Animals , Colon/pathology , Curcumin/pharmacokinetics , Drug Administration Routes , Edema/drug therapy , Edema/pathology , Hemorrhage/drug therapy , Hemorrhage/pathology , Humans , Inflammatory Bowel Diseases/pathology , Male , Necrosis/drug therapy , Necrosis/pathology , Rats
6.
Eur J Med Chem ; 77: 422-87, 2014 Apr 22.
Article in English | MEDLINE | ID: mdl-24685980

ABSTRACT

A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid part(.) The present review article offers a detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques. Over the years, the researchers have employed this technique to discover some promising chemical architectures displaying significant anticancer profiles. Molecular hybridization as a tool has been particularly utilized for targeting tubulin protein as exemplified through the number of research papers. The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin, phenstatins and vinca alkaloids have been utilized as one of the functionality of the hybrids and promising results have been obtained in most of the cases with some of the tubulin based hybrids exhibiting anticancer activity at nanomolar level. Linkage with steroids as biological carrier vector for anticancer drugs and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA interactive antitumor antibiotics derived from Streptomyces species in hybrid structure based drug design has also emerged as a potential strategy. Various heteroaryl based hybrids in particular isatin and coumarins have also been designed and reported to posses' remarkable inhibitory potential. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Design , Animals , Antineoplastic Agents/chemical synthesis , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Structure-Activity Relationship
7.
ScientificWorldJournal ; 2014: 438528, 2014.
Article in English | MEDLINE | ID: mdl-24605053

ABSTRACT

The aim of the present investigation is to develop and statistically optimize the osmotically controlled asymmetric membrane capsules of solid dispersion of lycopene. Solid dispersions of lycopene with ß-cyclodextrin in different ratios were prepared using solvent evaporation method. Solubility studies showed that the solid dispersion with 1 : 5 (lycopene : ß-cyclodextrin) exhibited optimum solubility (56.25 mg/mL) for osmotic controlled delivery. Asymmetric membrane capsules (AMCs) were prepared on glass mold pins via dip coating method. Membrane characterization by scanning electron microscopy showed inner porous region and outer dense region. Central composite design response surface methodology was applied for the optimization of AMCs. The independent variables were ethyl cellulose (X1), glycerol (X2), and NaCl (X3) which were varied at different levels to analyze the effect on dependent variables (percentage of cumulative drug release (Y1) and correlation coefficient of drug release (Y2)). The effect of independent variables on the response was significantly influential. The F18 was selected as optimized formulation based on percentage of CDR (cumulative drug release) of 85.63% and correlation coefficient of 0.9994. The optimized formulation was subjected to analyze the effect of osmotic pressure and agitational intensity on percentage of CDR. The drug release was independent of agitational intensity but was dependent on osmotic pressure of dissolution medium.


Subject(s)
Carotenoids/administration & dosage , Drug Delivery Systems , Carotenoids/chemistry , Lycopene , Microscopy, Electron, Scanning , Osmosis , Solubility
8.
EXCLI J ; 13: 137-50, 2014.
Article in English | MEDLINE | ID: mdl-26417248

ABSTRACT

In order to evaluate the role of ethyl acetate fraction (PB-EtAC) obtained from the Phyllostachys bambusoides leaves in the modulation of immune responses, detailed studies were carried out using a panel of in vivo assays. Oral administration of PB-EtAC (50-200 mg/Kg) stimulated the IgM and IgG titre expressed in the form of haemagglutination antibody (HA) titre. Further, it elicited a dose related increase in the delayed type hypersensitivity reaction (DTH) after 24 and 48 h in BALB/c mice. Besides augmenting the humoral and cell mediated immune response, the concentration of cytokines (IFN-γ, IL-2, and IL-4) in serum with respect to T cell interactions also increased significantly. It also induced macrophage phagocytosis, and nitric oxide (NO) production which resulted in a high degree of protection against Candida albicans and carbon clearance. Moreover, the enhancement in CD4 and CD8 cell populations as revealed by flow cytometry. Taken together this in vivo and ex vivo preclinical data, our results suggested that PB-EtAC acts as an effective immunostimulator eliciting both Th1 and Th2 immune responses. We are reporting first time the immunostimulatory potential of P. bambusoides and it might be regarded as a biological response modifier.

9.
Curr Drug Deliv ; 10(5): 564-71, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23360241

ABSTRACT

In the present investigation chitosan microspheres loaded with flurbiprofen (FLB) were prepared by oil/oil emulsification method for colon specific drug delivery. FLB was entrapped in chitosan microspheres, following coating with Eudragit S-100 utilizing the benefits of pH dependent solubility of Eudragit S-100, so as to prevent the premature release of FLB in upper GIT. Different batches of FLB microspheres were prepared by varying FLB: chitosan ratio (1:1 to 1:4). The effect of chitosan concentration on size, entrapment efficiency, percent drug loading and degree of swelling was evaluated. DSC studies revealed the dispersion of FLB in the matrix of chitosan microspheres. SEM analysis indicated the nearly smooth surface and spherical shape of the prepared microspheres. X-ray diffract gram of FLB microspheres showed less intense peaks as compared to free FLB. In vitro release studies of uncoated FLB- chitosan microspheres showed burst release in initial 4 h, while Eudragit S-100 coated microspheres prevented the premature release of FLB and showed controlled release for 12 h following Higuchi model, thus suitable for colon specific drug delivery.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Flurbiprofen/chemistry , Calorimetry, Differential Scanning , Chitosan/chemistry , Colon , Inflammatory Bowel Diseases , Microspheres , Polymethacrylic Acids/chemistry , X-Ray Diffraction
10.
Bioorg Med Chem ; 19(6): 1950-8, 2011 Mar 15.
Article in English | MEDLINE | ID: mdl-21353569

ABSTRACT

Xanthine oxidase is a complex molybdoflavoprotein that catalyses the hydroxylation of xanthine to uric acid. Fifty three analogues of 1-acetyl-3,5-diaryl-4,5-dihydro(1H)pyrazoles were rationally designed and synthesized and evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Some notions about structure activity relationships are presented. Six compounds 41, 42, 44, 46, 55 and 59 were found to be most active against XO with IC(50) ranging from 5.3 µM to 15.2 µM. The compound 59 emerged as the most potent XO inhibitor (IC(50)=5.3 µM). Some of the important interactions of 59 with the amino acid residues of active site of XO have been figured out by molecular modeling.


Subject(s)
Enzyme Inhibitors/chemical synthesis , Pyrazoles/chemistry , Xanthine Oxidase/antagonists & inhibitors , Binding Sites , Catalytic Domain , Computer Simulation , Drug Design , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Isomerism , Pyrazoles/chemical synthesis , Pyrazoles/pharmacology , Structure-Activity Relationship , Xanthine Oxidase/metabolism
11.
Bioorg Med Chem ; 18(15): 5626-33, 2010 Aug 01.
Article in English | MEDLINE | ID: mdl-20621497

ABSTRACT

A series of arylidene analogues of Meldrum's acid were synthesized and evaluated for in vitro antimalarial and antioxidant activities for the first time. The influence of various physico-chemical parameters such as dielectric constant (epsilon), donor number (DN), acceptor number (AN), hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), and solubilizing power of the solvents on Meldrum's acid anion generation and thus on promoting the Knoevenagel condensation of Meldrum's acid with aryl aldehydes has been discussed. Five compounds 9l, 9m, 9n, 9r, and 9s were found to be most active against Plasmodiumfalciparum with IC(50) values in the range of 9.68-16.11 microM. Compound 9l exhibited the most potent antimalarial activity (IC(50) 9.68 microM). The compounds were also found to possess antioxidant activity when tested against DPPH and ABTS free radicals.


Subject(s)
Antimalarials/chemical synthesis , Antioxidants/chemical synthesis , Dioxanes/chemistry , Animals , Antimalarials/chemistry , Antimalarials/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Dioxanes/chemical synthesis , Dioxanes/pharmacology , Hydrogen Bonding , Plasmodium falciparum/drug effects , Structure-Activity Relationship
12.
Indian J Pharm Sci ; 72(6): 801-6, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21969759

ABSTRACT

Chalcones and their synthetic analogues appear to have the same binding site of tubuline as phenstatin, combretastatin steganacin and podophylotoxin and are therefore capable to inhibit cancer cell proliferation. The phenyl rings with appropriate substitutions maintain a fixed distance between two centers of aryl rings. The two aromatic rings in these molecules are arranged like the two wings of a butterfly having certain dihedral angle between them, therefore a "butterfly model" is proposed an important structural feature responsible for their antitubulin activity. In this sequence a series of chalcones were synthesized and evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. In addition the synthetics reduced MIC of ciprofloxacin upto four fold this indicates their bioavailability enhancing potential.

13.
J Chromatogr Sci ; 44(5): 239-43, 2006.
Article in English | MEDLINE | ID: mdl-16774707

ABSTRACT

High-performance liquid chromatography (HPLC) with diode array detection interfaced to electrospray ionization (ESI) mass spectrometry (MS) is applied to identify the two epimers of a novel and minor constituent, podophyllotoxin-4-O-(D)-6-acetylglucopyraniside from high-altitude Podophyllum hexandrum for the first time. This is done by matching the structural information from the tandem MS data with the reported lignan markers. The results show that LC-MS-MS is the method of choice for fast detection and detailed chemical analysis of mixtures in the crude extracts of Podophyllum. The method can be employed in the absence of reference standards for the markers and is particularly useful in view of the scarcity of these rare chemical standards.


Subject(s)
Chromatography, Liquid/methods , Glucosides/chemistry , Podophyllotoxin/analogs & derivatives , Podophyllum/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods , Podophyllotoxin/chemistry
14.
Eur J Med Chem ; 41(3): 429-34, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16430993

ABSTRACT

Taking lead from a naturally occurring quinazolin vasicine, a number of compounds were developed and evaluated for bronchodilator and anti-allergic activities. One of these compounds was 2,4-diethoxy-6,7,8,9,10,12-hexahydroazepino[2,1-b]quinazolin-12-one, hereinafter named 95-4, exhibited marked bronchodilator activity evaluated on contracted trachea or constricted tracheo-bronchial tree. On intestinal smooth muscle too it showed relaxant effect. Tracheal relaxant effect was not found to be mediated through beta-adrenoceptors. Cumulative dose-response study with acetylcholine and histamine indicated for its non-specific direct effect on smooth muscles. 95-4 was found to be more potent than theophylline and less to that of salbutamol on dose basis. Tested by a number of experimental models, it was found devoid of anti-allergic activity. It was also found to be free from any adverse effect. 95-4 due to its marked bronchial muscle relaxant effect can find use in conditions associated with spasm of bronchial muscles.


Subject(s)
Azepines/chemical synthesis , Azepines/pharmacology , Bronchodilator Agents/chemical synthesis , Quinazolines/chemical synthesis , Alkaloids/chemical synthesis , Alkaloids/chemistry , Animals , Azepines/chemistry , Bronchodilator Agents/chemistry , Bronchodilator Agents/pharmacology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Guinea Pigs , Ileum/drug effects , Quinazolines/chemistry , Quinazolines/pharmacology
15.
Bioorg Med Chem ; 13(24): 6672-7, 2005 Dec 15.
Article in English | MEDLINE | ID: mdl-16198115

ABSTRACT

Phytochemical investigation of Datura quercifolia (Solanaceae) plant yielded a new datura lactone, 1beta,5alpha,12alpha-trihydroxy-6alpha,7alpha,24alpha,25alpha-diepoxy-20S,22R with-2-enolide (1), along with two known compounds, 2 and 3. The structure of 1 was established on the basis of spectral analysis, as well as by its chemical transformation into known datura lactones. These compounds have been evaluated for immunomodulatory activity by observing their effect on antibody production, T-cell and B-cell activation, and cytokine production from splenocytes. Compound 2 was found to be the most promising immunostimulator in the present study.


Subject(s)
Datura/chemistry , Immunologic Factors/immunology , Immunologic Factors/isolation & purification , Lactones/immunology , Lactones/isolation & purification , Animals , Hypersensitivity, Delayed/immunology , Immunologic Factors/chemistry , Immunologic Factors/pharmacology , Interleukin-2/biosynthesis , Lactones/chemistry , Lactones/pharmacology , Magnetic Resonance Spectroscopy , Mice , Mice, Inbred BALB C , Spleen/drug effects , Spleen/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Tumor Necrosis Factor-alpha/biosynthesis
16.
J Chromatogr Sci ; 43(7): 348-50, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16176645

ABSTRACT

The present work describes the isolation of camptothecin and 9-methoxycamptothecin from the aerial parts of Nothapodytes foetida by semipreparative high-performance liquid chromatography because the separation of compounds by conventional procedures is tedious and cumbersome. The purity of the isolates is determined by physicochemical data and liquid chromatography-mass spectrometry.


Subject(s)
Camptothecin/analogs & derivatives , Camptothecin/isolation & purification , Chromatography, High Pressure Liquid/methods , Magnoliopsida/chemistry , Chromatography, Liquid/methods , Mass Spectrometry/methods
17.
Bioorg Med Chem Lett ; 15(12): 3177-80, 2005 Jun 15.
Article in English | MEDLINE | ID: mdl-15893928

ABSTRACT

A series of substituted chalcones and their corresponding pyrazoles were synthesized and evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. Out of 93 compounds screened, 8 compounds, 1s, 3i,j,n, 4i,j,n and 4s, showed marked activity. Compounds 4j,n and 4s were found to be the most promising in this study. SAR is also discussed.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Chalcone/chemistry , Chalcone/pharmacology , Pyrazoles/chemistry , Pyrazoles/pharmacology , Antineoplastic Agents/chemical synthesis , Chalcone/chemical synthesis , Drug Screening Assays, Antitumor , Humans , Inhibitory Concentration 50 , Neoplasms/drug therapy , Pyrazoles/chemical synthesis , Tumor Cells, Cultured
18.
Bioorg Med Chem ; 8(1): 251-68, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10968285

ABSTRACT

Inhibitors of drug metabolism have important implications in pharmaco-toxicology and agriculture. We have reported earlier that piperine, a major alkaloid of black and long peppers inhibits both constitutive and inducible cytochrome P450 (CYP)-dependent drug metabolising enzymes. In the present study, an attempt has been made to prepare several novel synthetic analogues so as to relate various modifications in the parent molecule to the inhibition of CYP activities. Two types of mono-oxygenase reactions arylhydrocarbon hydroxylase (AHH) and 7-methoxycoumarin-O-demethylase (MOCD) have been studied. Inhibition studies were investigated in rat microsomal fraction prepared from untreated, 3MC- and PB- treated rat liver in vitro. Modifications were introduced into the piperine molecule: (i) in the phenyl nucleus, (ii) in the side chain and (iii) in the basic moiety. Thus, 38 compounds have been subjected to such studies, and simultaneously an attempt has also been made to arrive at the structure-activity relationship of synthetic analogues. In general, most of the inhibitory potential of the parent molecule is lost with modification in either of the three components of piperine. Saturation of the side chain resulted in significantly enhanced inhibition of CYP while modifications in the phenyl and basic moieties in few analogues offered maximal selectivity in inhibiting either constitutive or inducible CYP activities. Thus few novel analogues as CYP inactivators have been synthesized which may have important consequences in pharmacokinetics and bioavailability of drugs.


Subject(s)
Alkaloids , Cytochrome P-450 Enzyme System/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Microsomes, Liver/drug effects , Piperidines/chemistry , Piperidines/pharmacology , Animals , Benzodioxoles , Cytochrome P-450 Enzyme Inhibitors , Cytochrome P-450 Enzyme System/biosynthesis , Enzyme Induction , Enzyme Inhibitors/chemical synthesis , Kinetics , Male , Microsomes, Liver/enzymology , Piperidines/chemical synthesis , Polyunsaturated Alkamides , Rats , Spectrum Analysis , Structure-Activity Relationship , Tumor Cells, Cultured
19.
Phytochemistry ; 53(2): 305-9, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10680188

ABSTRACT

Three new triterpenoids, designated as koelpinin-A, B and C and characterised as 28-nor-lup-12,17-dien-3 beta,16 alpha-diol,3 beta-acetoxy-28-nor-lup-12,17-dien-16 alpha-ol and 28-nor-lup-12,17-dien-3 beta-ol-16-one, respectively, together with 30-nor-lup-3 beta-ol-20-one, taraxeryl acetate and germanicol, were isolated, from the aerial parts of Koelpinia linearis. 13C-NMR shifts were assigned after performing APT and DEPT experiments.


Subject(s)
Plants/chemistry , Triterpenes/chemistry , Models, Molecular , Molecular Conformation , Molecular Structure , Triterpenes/isolation & purification
20.
Indian J Gastroenterol ; 14(2): 51-3, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7797277

ABSTRACT

BACKGROUND: Zinc is essential for various metabolic processes of the body. Since serum zinc levels are lowered in liver diseases, it has been postulated to be a precipitating factor for hepatic encephalopathy. METHODS: We prospectively studied serum zinc levels in consecutive patients with fulminant hepatic failure, subacute hepatic failure and chronic liver disease with encephalopathy. Serum zinc levels were correlated with various clinical and biochemical parameters and final outcome of patients. Serum zinc levels were estimated by atomic absorption spectrometry at admission and also 24 hours after recovery in survivors. RESULTS: Of the 55 patients (age 17-65 years, 35 men) studied, 30 had acute, 5 subacute and 20 chronic liver disease. Patients with hepatic encephalopathy had significantly lower serum zinc levels as compared to 20 age and sex matched controls. High serum bilirubin levels and prothrombin time showed inverse relationship with serum zinc levels. There was no relationship of serum zinc levels with age, sex, grade and duration of encephalopathy, liver size, ascites or splenomegaly. CONCLUSIONS: Hepatic encephalopathy is associated with low serum zinc levels. Recovery occurred in 17 patients despite persisting low serum zinc levels. Serum bilirubin > 23 mg/dL and prothrombin time prolongation > 12 seconds above control have inverse correlation with serum zinc level.


Subject(s)
Hepatic Encephalopathy/blood , Zinc/blood , Adult , Chronic Disease , Female , Humans , Liver Diseases/blood , Liver Failure/blood , Male , Prospective Studies , Spectrophotometry, Atomic
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