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Background: Machine learning has become an essential tool for drug research to generate pertinent structural information to design drugs with higher biological activities. Quantitative structureactivity relationship (QSAR) is considered one technique. QSAR study involves two main steps: first is the generation of descriptors, and the second is building and validating the models. Aim: By using a Python program language for building the QSAR model of pyrazoline derivatives, the data were collected from diverse literature for the inhibition of Mycobacterium tuberculosis. Pyrazoline, a small molecule scaffold, could block the biosynthesis of mycolic acids, resulting in mycobacteria death and leading to anti-tubercular drug discovery. Methods: We have developed a new Python script that effectively uses CDK descriptor as the independent variable and anti-tubercular bioactivity as the dependent variable in building and validating the best QSAR model. The built QSAR model was further cross-validated by using the external test set compounds. Then, the three algorithms, viz. multiple linear regression, support vector machine, and partial least square classifiers, were used to differentiate and compare their r2 values. Results: Our generated QSAR model via an open-source python program predicted well with external test set compounds. The generated statistical model afforded the ordinary least squares (OLS) regression as R2 value of 0.514, F value of 5.083, the adjusted R2 value of 0.413, and std. error of 0.092. Moreover, the multiple linear regression showed the R2 value of 0.5143, reg.coef_ of, -0.07795 (PC1), 0.01619 (PC2), 0.03763 (PC3), 0.07849 (PC4), -0.09726 (PC5), and reg.intercept_ of 4.8324. The performance of the model was determined by the support vector machine classifier of sklearn, module and it provided a model score of 0.5901. Further, the model performance was supported by a partial least square regression, and it showed the R2 value of 0.5901. The model performance was validated, and the model predicted similar values when compared to that of the train set, and the plotted linear curve between the predicted and actual pMIC50 value showed all data to fall over the middle linear line. Conclusion: We have found that the model score obtained using this script via three diverse algorithms correlated well, and there was not much difference between them; the model may be useful in the design of a similar group of pyrazoline analogs as anti-tubercular agents.

Background: Chronic non communicable diseases were interlinked with inflammation and infections should response to starting core of major diseases in both acute and chronic conditions. In drug discovery, development of a drug which acts as anti-infective agents (anti-microbial and anti-inflammatory) must be ideal and challenging for management of many chronic diseases. Objective: In this study, six lead pyrazoline hybrids were synthesized by cyclization of chalcones and characterized by various spectroscopic and elemental analysis. All synthesized compounds were screened for anti-inflammatory and anti-microbial activity by computational tools and biological evaluation. Methods: Synthesized pyrazoline analogues were characterized by various spectroscopic techniques and evaluated for prediction of pharmacokinetics, physicochemical properties and Molecular docking studies of various targeted enzymes on microbial and inflammatory mediators. Those compounds were screened by anti-microbial and anti-inflammatory activities by several in-vitro and in-vivo methods. Results: The synthesized compounds (A1-A6) were screened for anti-inflammatory activity in which compound A2 produced effective percentage inhibition (45.8 %) potent activity compared with that of standard indomethacin (49.7 %) in carrageenan paw edema method were observed. The anti-microbial activity was screened on synthesized compounds, among which A3 [2-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-5-yl) phenol, A2 [5-(4-chlorophenyl)-1,3-diphenyl-4,5-dihydro-1H-pyrazole] produced potential percentage zone of inhibition between 80 - 70 % for bacterial strains and 94 - 89 % for fungal strains were observed. The minimum inhibitory concentration values of those compounds were 1.56 to 6.25 µg/ml for bacterial strains and 1.56 to 12.5 µg/ml for fungal strains were noted compared with the standard gatifloxacin and clotrimazole, respectively. The molecular docking, pharmacokinetics and toxicity predictions on those compounds were supported further for the development of potent anti-infective agents. Conclusion: The hypothesis of this research was correlated with the results of anti-inflammatory and anti-microbial activity. The binding interactions of respective enzymes were coincided with reduction of paw edema in anti-inflammatory model and zone of inhibition in anti-microbial activity were observed.

Diabetes Mellitus is a leading community health agony. Although steady new drug evolution to care intended for diabetes, herbal remedy stay a prospective add-on remedy to maintain glucose level in the body. Moringa oleifera (Moringaceae) has been conventionally used to deal with numerous diseases as the anti-oxidant properties it reports. The effect M. oleifera stem bark extracts against diabetes alloxanized diabetic rats were employed in this research. Bark of M. oleifera stem was used. Male Wistar albino rats (150–200g) were employed. Blood samples were accumulated by retro-orbital plexus puncture method and blood glucose of all animals was examined by means of an electronic glucometer. Diabetes commences due to Alloxan during its capability to demolish the insulin-generating beta cells of the pancreas. Three weeks observations indicate drop in blood glucose levels as in Alloxan + glibenclamide (10mg/kg) used as standard from 295mg/dl to 149mg/dl. Alloxan + Methanolic extract of M. oleifera (100mg/kg) from 294 mg/dl to 237mg/dl. Alloxan + Methanolic extract of M. oleifera (200mg/kg) from 295mg/dl to 232mg/dl. Alloxan + Methanolic extract of M. oleifera (400 mg/kg) from 290mg/dl to 229mg/dl. Three weeks of daily treatment of extract of M. oleifera led to a dose dependent fall in blood sugar in three weeks for methanolic extract of M. oleifera. The current research concludes that extracts of M. oleifera bark is able to demonstrate drop in blood glucose level in normal and alloxan treated rats.

Background: Drug discovery requires the use of hybrid technologies for the discovery of new chemical substances. One of those interesting strategies is QSAR via applying an artificial intelligence system that effectively predicts how chemical alterations can impact biological activity via in-silico. Aim: Our present study aimed to work on a trending machine learning approach with a new opensource data analysis python script for the discovery of anticancer lead via building the QSAR model by using 53 compounds of thiazole derivatives. Methods: A python script has been executed with 53 small thiazole chemicals using Google collaboratory interface. A total of 82 CDK molecular descriptors were downloaded from “chemdes” web server and used for our study. After training the model, we checked the model performance via cross-validation of the external test set. Results: The generated QSAR model afforded the ordinary least squares (OLS) regression as R2 = 0.542, F=8.773, and adjusted R2 (Q2) =0.481, std. error = 0.061, reg.coef_ developed were of, - 0.00064 (PC1), -0.07753 (PC2), -0.09078 (PC3), -0.08986 (PC4), 0.05044 (PC5), and reg.intercept_ of 4.79279 developed through stats models, formula module. The performance of test set prediction was done by multiple linear regression, support vector machine, and partial least square regression classifiers of sklearn module, which generated the model score of 0.5424, 0.6422 and 0.6422 respectively. Conclusion: Hence, we conclude that the R2values (i.e. the model score) obtained using this script via three diverse algorithms were correlated well and there is not much difference between them and may be useful in the design of a similar group of thiazole derivatives as anticancer agents.

A novel series of chalcone bearing pyrazoline moieties were (P1 to P7) synthesized and characterized by various analytical techniques. The anti-inflammatory studies showed the compounds P1, P2, P5, and P6 have produced the noteworthy inhibition on protein denaturation (81.39 - 96.57 %) when compared to standard 98.17% whereas, the antiproteinase activity was in the range of 84.55- 90.44 % when compared to the standard, 95.95 %. The compounds, P1, P2, P5 (2-Cl, 4- Cl & -NO2 substituent) bearing electron-withdrawing groups and the compounds P3 & P6 (4-N(CH3)2 & -OH substituent) possessing electron-donating group in its phenyl ring system exhibited the prominent activity. Further, to explore the molecular mechanism, the in-silico docking study against COX-2 enzyme was performed. The compounds were also screened for their antibacterial activities. Among them, the compounds P1, P2, P3, P5 and P6 showed the significant antibacterial activity against both gram-positive and gram-negative pathogen such as, Bacillus cereus, Staphylococcus aureus, Serratia marcescens and Staphylococcus typhi with maximum zone of inhibition within the range of 12-14 mm and 19-25 mm for 100 and 200 µg/ml concentrations respectively when compared to that of standard drug Gentamycin, whose ranges between 15-18 mm and 25-28 mm correspondingly.

ITO nanoparticles were obtained by combustion reaction of urea as fuel. The gel form structures were fired at 350°C in furnace for 20 min to yield powdery products and these products were calcined to five different temperatures from 100°C to 500°C for an hour to yield ITO powders. From the scanning electron microscopy (SEM) photographs and particle size analysis the average sizes of the cubic particle of powders are found to be less than 15 nm and less than 20 nm respectively. The ratio of doping concentration In/Sn is 90/10 and 80/20. The X-ray diffraction (XRD) data were evaluated by Scherer equation for the estimation of the average crystal size of the powders (less than 20 nm) for 90/10 and (less than 25 nm) for 80/20. The synthesized ITO powder characterized by XRD, UV-Vis-NIR and PL shows high specific surface area and possesses small primary crystallite size and good optical band gap.

A simple, rapid, specific, sensitive and liquid chromatography coupled with tandem mass spectrophotometric method was developed and validated for the estimation of azathioprine and its metabolite 6-mercaptopurine in human plasma by using lamivudine and 6-mercaptopurine D3 as the internal standard. Azathioprine and 6-mercaptopurine were extracted from human plasma by solid-phase extraction (SPE)-Evaporation method, using Oasis MCX cartridge for cleaning procedure. The stationary phase was chromatographed on a ZORBAX SB CN, (75X50 mm, 5 µ) column where as mobile phase constitutes of acetonitrile: 2mM ammonium acetate (70:30 v/v) at a flow rate of 0.800 ml/min. The detection was performed with an Applied Biosystems Sciex API 4000 mass spectrometer by multiple reaction monitoring (MRM). The method validation proofs were carried out as per the USFDA guidelines as described, showing a linearity system (r2 > 0.99) over a range of 2.455 ng/mL to 106.568 ng/mL for azathioprine and 1.165 ng/mL to 101.143 ng/mL concentrations for 6-mercaptopurine and a recovery shows 99.36% and 100.44% for azathioprine and 6-mercaptopurine respectively. The results show that this proposed approach is effective and can be applied to the extraction and analysis of other pharmaceutical compounds.DOI: http://dx.doi.org/10.3329/icpj.v1i11.12059 International Current Pharmaceutical Journal 2012, 1(11): 342-352

A series of mononuclear Ru(II) complexes of the type [Ru(M) 2 (U)] 2+ , where M=2,2′-bipyridine/1,10-phenanthroline and U=tpl (Ru1), 4-Cl-tpl (Ru2), 4-CH 3 -tpl (Ru3), 4-CH 3 O-tpl (Ru4), and 4-NO 2 -tpl (Ru5), -pai (Ru6), where tpl = thiopicolinanilide and pai = 2-phenyl-azo-imidazole, have been prepared and characterized by IR, UV–Vis, 1 H NMR, 13 C-NMR, FAB-Mass spectrophotometer, and elemental analysis. The complexes display metal–ligand charge transfer (MLCT) transitions in the visible region. The title complexes were subjected to in vivo anticancer activity tests against a transplantable murine tumor cell line, Ehrlich’s ascitic carcinoma (EAC) and in vitro antibacterial activity against Gram positive and Gram negative microorganisms. Ru1–Ru6 were found to increase the life span of the tumor hosts by 19–52%, and decreased tumor volume and viable ascitic cell count. The results of the present study clearly demonstrated the tumor inhibitory activity of the ruthenium chelates against transplantable murine tumor cell line. The treatment with ruthenium complexes could be secondary to tumor regression or due to the action of the compounds itself. The significant antibacterial activity was observed for Ru1–Ru4 against microorganisms like Vibrio cholera 865, Staphylococcus aureus 6571, and Shigella flexneri as compared to that of standard drug chloramphenical. Ru5 showed moderate activity against S. aureus 8530. However, all the complexes fail to show significant antibacterial activity against V. cholera 14033 and Shigella sonnai .

The antioxidant defense system dramatically controls hepatocellular carcinoma induced by N.-nitrosodiethylamine (NDEA). In order to assess the anticarcinogenic activity of a methanol extract of Caesalpinia bonducella. (MECB) leaves containing flavonoids and triterpenoids, the antioxidant defense system has been evaluated. The effect of MECB on lipid peroxidation end-product malondialdehyde (MDA), enzymatic antioxidants such as superoxide dismutase (SOD) and catalase (CAT), and nonenzymatic antioxidants glutathione (GSH), vitamin E, and vitamin C levels were analyzed in the liver of control and experimental animals. Serum was also analyzed for transaminase activity (SGOT and SGPT), alkaline phosphatase (SALP), bilirubin, total protein, and uric acid. Depletion of all these antioxidants was recorded in cancer conditions. These deleterious effects are controlled by the administration of MECB. After drug administration, there was a marked increase in antioxidant levels and a dramatic decrease in lipid...

Background & objectives: Derivatives of isatin are known to have cytotoxicity against human carcinoma cell lines. This compound therefore, has a potential to be used as a chemotherapeutic agent against cancer. This study was done to investigate the antioxidant and anticancer activities of isatin, extracted from flower of a folklore medicinal plant Couroupita guianensis against human promylocytic leukemia (HL60) cells. Methods: Active fractions demonstrating anticancer and antioxidant activities were isolated from the extracts of shade-dried flowers of C. guianensis by bioassay guided fractionation. The free radical scavenging activity was determined using lipid peroxidation assay. Cytotoxicity against human promylocytic leukemia HL60 cells was determined by MTT assay. Apoptotic activity was analyzed by DNA fragmentation and flowcytometry. Results: Isatin isolated from the active fraction showed antioxidant activity with the EC50 value of 72.80 μg/ml. It also exhibited cytotoxicity against human promylocytic leukemia HL60 cells in dose-dependant manner with the CC50 value of 2.94 μg/ml. The isatin-treated cells underwent apoptosis and DNA fragmentation. Apoptosis was confirmed by the FACS analysis using FITC-annexin V markers. Interpretation & conclusions: Isatin showed antioxidant activity and was cytotoxic to the HL60 cells due to induction of apoptosis. The isatin can be further evaluated to be used as a prophylactic agent to prevent the free radical-induced cancer and as a chemotherapeutic agent to kill the cancer cells.

The aim of this study is to investigate the antioxidant defense system induced by the methanol extract of Bauhinia racemosa L.(MEBR) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis in Wister albino rats. The effects of MEBR on surface visible macroscopic (Morphometry) liver lesions (neoplastic nodules) and the levels of serum enzymes, lipid peroxidation and antioxidants were evaluated in NDEA-induced hepatocarcinogenesis in rats.In rats treated, with NDEA, significantly elevated levels of serum enzymes (SGOT, SGPT and ALP), bilirubin and decreased levels of protein and uric acid were observed. Significantly elevated amount of malondialdehyde (MDA), the end product of lipidperoxidation, indicated higher levels of lipid peroxidation, which was accompanied by significantly decreased levels of antioxidants like vitamin C, vitamin E, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Administration of MEBR was able to suppress nodule development/hepatocellular lesion formation in rats. The extract treatment increases in antioxidant levels and dramatic decreases in lipid peroxidation levels. MEBR also produced a protective effect by decreasing the level of serum enzymes, bilirubin and increased the protein and uric acid levels. The results suggest that MEBR exert chemopreventive effects by suppressing nodule development and decreasing lipid peroxidation and enhancing the levels of antioxidants in NDEA carcinogenesis by reducing the formation of free radicals.

The present study was carried out to evaluate the anti-inflammatory and analgesic activities of methanol extract of Careya arborea (MECA). The effects of MECA on the acute and chronic phases of inflammation were studied in carrageenan, dextran and mediators (histamine and serotonin) induced paw oedema and cotton pellet induced granuloma respectively. Analgesic effect of MECA was evaluated in acetic acid induced writhing and hotplate tests. The anti-oedema effect of MECA was compared with indomethacin 10 mg/kg orally. In acute phase of inflammation a maximum inhibition of 50.56, 48.86, 47.12 and 48.23% (p Keywords : Careya arborea , anti-inflammatory, analgesic, rat, mice Nigerian Journal of Natural Products and Medicine Vol. 9 2005: 38-43

The present study was carried out to evaluate the antioxidant and antimicrobial activities of a methanol extract of Bauhinia racemosa (MEBR) (Caesalpiniaceae) stem bark in various systems. 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radical, superoxide anion radical, nitric oxide radical, and hydroxyl radical scavenging assays were carried out to evaluate the antioxidant potential of the extract. The antioxidant activity of the methanol extract increased in a concentration-dependent manner. About 50, 100, 250, and 500 microg MEBR inhibited the peroxidation of a linoleic acid emulsion by 62.43, 67.21, 71.04, and 76.83%, respectively. Similarly, the effect of MEBR on reducing power increased in a concentration-dependent manner. In DPPH radical scavenging assays the IC50 value of the extract was 152.29 microg/ml. MEBR inhibited the nitric oxide radicals generated from sodium nitroprusside with an IC50 of 78.34 microg/ml, as opposed to 20.4 microg/ml for curcumin. Moreover, MEBR scavenged the superoxide generated by the PMS/NADH-NBT system. MEBR also inhibited the hydroxyl radical generated by Fenton's reaction, with an IC50 value of more than 1000 microg/ml, as compared to 5 microg/ml for catechin. The amounts of total phenolic compounds were also determined and 64.7 microg pyrocatechol phenol equivalents were detected in MEBR (1 mg). The antimicrobial activities of MEBR were determined by disc diffusion with five Gram-positive, four Gram-negative and four fungal species. MEBR showed broad-spectrum antimicrobial activity against all tested microorganisms. The results obtained in the present study indicate that MEBR can be a potential source of natural antioxidant and antimicrobial agents.

Analgesic, antipyretic activity and toxicity study of the leaves of Bryonia laciniosa Linn. (Family: Cucurbitaceae) was evaluated in the standard animal models. The methanol extract of Bryonia laciniosa (MEBL) was evaluated by hot plate and acetic acid-induced writhing methods to assess analgesic activity. The antipyretic activity of the extract was also evaluated by normal body temperature and yeast-induced hyperpyrexia. The extract showed significant analgesic and antipyretic activity. The MEBL was further evaluated for toxicity at the doses of 125 and 250 mg/kg administered orally for 14 days in rats. At the end of experiments, the blood, liver function and kidney metabolism were observed. The hematological profile and different biochemical parameters such as SGOT, SGPT and ALP were estimated. The present study revealed that MEBL exhibited significant analgesic and antipyretic activity in the tested experimental animal models. The toxicity study indicates that the extract is not toxic at the tested doses.