Drug Development and Therapeutics最新文献

{"title":"Acute porphyria: The drug demon etiology","authors":"S. Kannan, S. Gowri","doi":"10.4103/2394-6555.162436","DOIUrl":"https://doi.org/10.4103/2394-6555.162436","url":null,"abstract":"Drugs are one of the important factors that precipitate acute attacks in patients with porphyria. Various in vitro and preclinical animal models exist for determining porphyrogenicity of a drug, but these predictions are not very reliable. Ambiguities still remain with many drugs as to whether they are safe in patients with porphyria. An algorithm for determining the porphyrogenic potential using evidence from anectodotal reports, lipophilicity, affinity of a drug to the Cytochrome enzymes (CYP450), ability to induce or irreversibly inhibit either CYP450 2C9 or CYP450 3A4 and the ability to induce hepatic 5-aminolevulinate synthase has been devised. Management of an acute attack of porphyria involves symptomatic treatment and administration of haem arginate. Several international networks have been initiated that serve as good sources of information for the safe use of drugs to be used in porphyria.","PeriodicalId":11347,"journal":{"name":"Drug Development and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79932263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization and expression of folate receptor-α in T47D human breast cancer cells","authors":"Jwala Renukuntla, Sujay J. Shah, S. H. Boddu, A. Vadlapudi, R. Vadlapatla, D. Pal, A. Mitra","doi":"10.4103/2394-6555.162441","DOIUrl":"https://doi.org/10.4103/2394-6555.162441","url":null,"abstract":"Purpose: The objective of this study was to investigate the functional and molecular expression of a carrier mediated system responsible for folate uptake in breast cancer (BC) (T47D) cells and to delineate the mechanism of intracellular regulation of this transport system. Materials and Methods: [ 3 H]-folic acid uptake was studied in T47D cells with respect to time, pH, temperature, sodium and chloride ion dependency. Inhibition studies were conducted in the presence structural analogs, vitamins, metabolic and membrane transport inhibitors. [ 3 H]-folic acid uptake was also determined with varying concentrations of cold folic acid. Uptake kinetics was studied in the presence of various modulators of intracellular regulatory pathways; calcium-calmodulin, protein kinases A and C (PKA and PKC) and protein tyrosine kinase (PTK). Molecular evidence was studied by qualitative and quantitative polymerase chain reaction (PCR) and Western blot analysis. Results: Linear increase in [ 3 H]-folic acid uptake was observed over 30 min. The process followed saturation kinetics with an apparent K m of 11.05 nM, V max of 1.54 FNx01 10−8 μmoles/min/mg proteins and K d of 9.71 FNx01 10−6 /min for folic acid. Uptake process was found to be dependent on pH, sodium ions, chloride ions, temperature and energy. Uptake was inhibited in the presence of structural analogs (cold folic acid, methyltetrahydro folate and methotrexate), but structurally unrelated vitamins did not show any effect. Membrane transport inhibitors such as SITC, DIDS, probenecid and endocytic inhibitor colchicine significantly inhibited the [ 3 H]-folic acid uptake process. PKA, PTK and Ca 2+ /calmodulin pathways positively regulate the uptake process. Reverse transcriptase polymerase chain reaction (RT PCR) analysis had shown mRNA expression of folate receptor (FR)-α at 407 bp. Quantitative polymerase chain reaction analysis showed significantly higher FR-α mRNA levels in T47D cells compared to MCF-7 cells and Western blot analysis confirmed the FR-α protein expression at 37 kDa. Conclusions: This work demonstrated the functional characterization and molecular presence of FR-α in the T47D cell line. The high expression of FRs in T47D human breast carcinoma cells supports their validity as molecular therapeutic targets in BC.","PeriodicalId":11347,"journal":{"name":"Drug Development and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85168898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic susceptibility pattern of Salmonella enterica serovar typhi and Salmonella enterica serovar paratyphi A with special reference to quinolone resistance","authors":"S. M. Rudresh, T. Nagarathnamma","doi":"10.4103/2394-6555.162448","DOIUrl":"https://doi.org/10.4103/2394-6555.162448","url":null,"abstract":"Background and Objectives: Typhoid fever is endemic in India. Extensive use of first-line antibiotics has led to the emergence of multi-drug resistant (MDR) Salmonella typhi. Ciprofloxacin has become empirical therapy of choice against MDR salmonellae. Recent year′s emergence of low-level ciprofloxacin resistance in salmonellae resulted in delayed response and serious complications. Nalidixic acid (NA) screen test is used as surrogate marker for detection low-level ciprofloxacin resistance. In this study, we evaluated prevalence of MDR and low-level ciprofloxacin resistant S. typhi and Salmonella paratyphi A. Materials and Methods: A total of 50 blood culture isolates of S. typhi and S. paratyphi A were tested for antibiotic susceptibility according to Clinical Laboratory Standards Institute (CLSI) method. Minimal inhibitory concentration (MIC) to ciprofloxacin was carried out by E-test and agar dilution method. Results: Among the 50 salmonella isolates, 80% were S. typhi and 20% were S. paratyphi A. MDR was found in 2% S. typhi. NA resistant salmonellae showed ciprofloxacin MIC ranging from 0.25 to 0.75 μg/ml. One isolate of S. typhi showed ciprofloxacin MIC of 32 μg/ml and was also resistant to ceftriaxone. NA screen test for low-level ciprofloxacin resistance was 100% sensitive and 97.9% specific. Interpretation and Conclusion: NA resistant isolates should be tested for ciprofloxacin MIC to decide therapeutic options. The current CLSI breakpoints may have to be re-evaluated for salmonellae.","PeriodicalId":11347,"journal":{"name":"Drug Development and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85274953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-vitro antimicrobial screening and molecular docking studies of synthesized 2-chloro-N-(4-phenylthiazol-2-yl)acetamide derivatives","authors":"Rahmat Ali, Suresh Kumar, O. Afzal, Sandhya Bawa","doi":"10.4103/2394-6555.162452","DOIUrl":"https://doi.org/10.4103/2394-6555.162452","url":null,"abstract":"Introduction: Glucosamine-6-phosphate (GlcN6P) synthase biosynthetic pathway has been identified as potential targets for the development of new antimicrobial agents. Aim: A series of 2-chloro-N-(42-phenylthiazol-25-yl)acetamide derivatives (3a-r) was synthesized and evaluated their antimicrobial activity. Materials and Methods: The 2-chloro-N-(Para substituted phenylthiazol-25-yl) acetamide (2a-c) were synthesized by stirring intermediates (1a-c) with 2-chloroacetylchloride in dichloromethane in the presence of K2CO3. The intermediate (2a-c) were further reacted with different secondary amine such as pyrrolidine, N-methyl piperazine, N-ethyl piperazine, thiomorpholine, morpholine, piperidine etc in ethanol in presence of TEA Triethylamine (TEA) to get desired compounds (3a-r). Compounds were characterized by a spectroscopic technique such as Fourier transform infraredFTIR, 1 H-NMR, 13 C-NMR, and mass spectrometry. The synthesized thiazole derivatives (3a-r) were screened for anti-bacterial and anti-fungal activity against Escherichia coli, Staphylococcus aureus NCTC 6571, Pseudomonas aeruginosa NCTC 10662, CandidaC. albicans (MTCC-183), AspergillusA. niger (MTCC 281) NCTC 10418 and AspergillusA. flavus (MTCC 277). Result and Conclusion: The results of anti-bacterial screening revealed that among all the screened compounds, eight compounds viz. 3b, 3c, 3d, 3e, 3i, 3j, 3k, and 3p showed moderate to good anti-bacterial and antifungal activity having minimum inhibitory concentration (MIC) between 6.25- and 25 µg/ml. While compound 3d showed the most promising antibacterial activity against E. coli and S. aureus, while the compound 3j showed promising antifungal activity with MIC value 6.25 µg/ml against C. albicans, A. niger and A. flavus. In addition, all these eight potential molecules were also examined for possible binding on enzyme GlcN6Pglucosamine-6-phosphate synthase by molecular docking studies on (PDB ID 1JXA).","PeriodicalId":11347,"journal":{"name":"Drug Development and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88385540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of antifungal activity of aqueous extracts of some medicinal plants against Aspergillus flavus, pistachio aflatoxin producing fungus in vitro","authors":"Sahar Omidpanah, H. Sadeghi, Mehdi Mohamadian Sarcheshmeh, A. Manayi","doi":"10.4103/2394-6555.162446","DOIUrl":"https://doi.org/10.4103/2394-6555.162446","url":null,"abstract":"Background: Contamination with aflatoxin, by Aspergillus flavus, is one the major challenges in agriculture and food industry. Preparation of organic products using natural components is widely considered these days. Aims: In this study, effects of aqueous extracts of five medicinal herbs, including thyme, senna, mentha, basil, and safflower on the growth of the A. flavus were investigated. Mterials and Methods: The extracts with different concentrations (200-800 µg/mL) and polyethylene glycol with the equal osmotic potential of plant extracts were added to the potato dextrose agar medium to evaluate fungus growth after 7 days using agar dilution method. Benomyl, a fungicide, was used as a positive standard. The tests were performed in triplicate, and the mean diameters of fungus growth were calculated as well. Results and Conclusion: All concentrations of the plants extracts significantly inhibited the fungus growth in comparison with each other and control treatments, while the extracts of thyme and safflower manifested the most effective prohibition compared to benomyl with minimum inhibitory concentration of 200 and 400 µg/mL, respectively.","PeriodicalId":11347,"journal":{"name":"Drug Development and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76803699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A green analytical method for the simultaneous analysis of cefixime trihydrate and ambroxol HCl based on ultraviolet derivative spectroscopy","authors":"Ceema Mathew, Suman Naik Bhukya, A. Makula, R. Puvvadi","doi":"10.4103/2394-6555.162450","DOIUrl":"https://doi.org/10.4103/2394-6555.162450","url":null,"abstract":"Context: Until date, there is no reported derivative spectrophotometric method for the combination of cefixime trihydrate (CEF) and ambroxol HCl (ABH). So an urgent need was felt to develop an ultraviolet (UV) derivative spectroscopic method, which reduces the cost of analysis on comparing with high-performance liquid chromatography or high-performance thin layer chromatography method. Aims: To develop and validate an economical and ecofriendly derivative spectroscopic method that avoids the use of organic solvents for simultaneous quantification of both the drugs. Materials and Methods: A simple method based on the derivative spectrophotometric method at zero crossing wavelengths has been developed for the simultaneous quantification of CEF and ABH. As the method depends on hydrotropic dissolution, 0.1N urea is used as the solvent, and it yields an economical and ecofriendly method. Two wavelengths 253 nm (zero crossing point (ZCP) for CEF) and 306 nm (ZCP for ABH) were selected for the quantification of ABH and CEF respectively. Results: The first derivative amplitude-concentration plots were linear over the range of 5-35 μg/ml and 3-10.5 μg/ml with detection limits of 0.187 and 0.0937 μg/ml and quantification limits of 0.625 and 0.312 μg/ml for CEF and ABH respectively. The percentage recovery was within the range between 99.05% and 102%. The % relative standard deviation for precision and accuracy of the method was found to be <2%. Conclusion: The proposed method was found to be simple, accurate and precise and can be successfully applied to the routine quality control analysis of studied drugs in their tablet formulations.","PeriodicalId":11347,"journal":{"name":"Drug Development and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74941284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoprotective effects of aqueous root bark extracts of Anogeissus leiocarpus, Terminalia avicennioides, and their mixture in diethylnitrosamine-treated rats","authors":"A. Salau, M. Yakubu, A. Oladiji","doi":"10.4103/2394-6555.162454","DOIUrl":"https://doi.org/10.4103/2394-6555.162454","url":null,"abstract":"Introduction: This study investigated the hepatoprotective activity of aqueous root bark extracts of Anogeissus leiocarpus, Terminalia avicennioides, and their 1:1 mixture in diethylnitrosamine (DEN)-treated rats. Materials and Methods: Rats were orally pretreated with extracts and 1:1 mixture (200, 400, and 800 mg/kg body weight) for 2 weeks before being challenged with DEN (30 mg/kg body weight) once a week on weeks 3 and 4. Curcumin (200 mg/kg body weight) was used as reference antioxidant agent, and distilled water was used as a control. The whole experiment lasted for 4 weeks. The activities of liver and serum alkaline phosphatase (ALP), aspartate and alanine aminotransferases (AST and ALT), and gamma-glutamyltransferase (GGT), as well as the levels of serum total protein, albumin, total, and conjugated bilirubin were evaluated. Results: The extracts and their mixture significantly (P < 0.05) prevented the DEN-induced alterations in the activities of ALP, AST, ALT, and GGT in the liver and serum of the animals; as well as the altered levels of serum total and conjugated bilirubin. Conclusion: Overall, the results of this study revealed that the extracts possess hepatoprotective activities against DEN-induced liver damage in rats.","PeriodicalId":11347,"journal":{"name":"Drug Development and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83423360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amlodipine potentiates the protective effect of zonisamide on pentylenetetrazol-induced kindling in mice","authors":"Mahfooz Alam, B. Singh, Vinay Kumar","doi":"10.4103/2394-6555.162453","DOIUrl":"https://doi.org/10.4103/2394-6555.162453","url":null,"abstract":"Background: Zonisamide (ZON) and amlodipine (AML) were studied in different experimental models of epilepsy individually. However, combination of ZON and AML has not been explored yet. Hence, this study was aimed to evaluate the combination therapy of ZON and AML on pentylenetetrazol (PTZ)-induced kindling in mice. Materials and Methods: Swiss albino mice of either sex were randomly divided into five groups and each group containing 8 mice. Kindling was induced by PTZ (45 mg/kg/day on 8 th , 10 th and 12 th and 75 mg/kg/day on 14 th day). After treatment animals were observed for 30 min for behavioral analysis then animals were sacrificed and brain was taken out for biochemical analysis. Results: PTZ-significantly induced seizure was characterized by alteration in seizure score and latency as well as significantly increased in brain thiobarbituric acid reactive substance (TBARS) levels and significantly decreased in reduced glutathione, catalase (CAT) and superoxide dismutase (SOD). Treatment with ZON and AML significantly (P < 0.05, P < 0.01 and P < 0.001) resorted seizure score, latency, TBARS, reduced glutathione, CAT and SOD near to normal compared with pentylentetrazol treated rats. Conclusion: This study provides experimental evidence that treatment with both ZON and AML attenuated seizure and oxidative stress in PTZ-induced kindling mice.","PeriodicalId":11347,"journal":{"name":"Drug Development and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83191689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrophotometric method for estimation of amiloride in bulk and tablet dosage form","authors":"A. Lakshmi","doi":"10.4103/2394-6555.162443","DOIUrl":"https://doi.org/10.4103/2394-6555.162443","url":null,"abstract":"Introduction: Amiloride chemically, 3,5-diamino-6-chloro-N-(diaminomethylene) pyrazine-2-carboxamide. It is used in the management of congestive heart failure, available as Amifru tab, Amimide. It causes adverse effects like Nausea, diarrhea and dizziness. Materials: 0.1 N Hydrochloric acid, 0.1 N Sodium hydroxide and 1 mg/ml amiloride drug solution were required. Spectral and absorbance measurements were made using ELICO UV-160 double beam Spectrophotometer. Method: Amiloride drug solution concentration range of 25 to 125ug/ml in 0.1N HCl medium was scanned over the wave length range of 235-320 against blank prepared in 0.1N NaOH solution. Two wavelengths are selected one at positive peak 245 nm and another at negative peak 290 nm, the amplitude is calculated from these values. Results and Discussion: The sum of the absolute values at these wavelengths is called amplitude. The amplitude is proportional to the amount of drug. High accuracy, reproducibility and low t-values were reported from the calibration curve plotted with the amplitude verses amount of drug. So the proposed method is simple, less time consuming and it can be successfully adopted for the estimation of amiloride.","PeriodicalId":11347,"journal":{"name":"Drug Development and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80955786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, syntheses, characterization, and evaluation of 2-substituted-1,3-bis(1-naphthylmethyl)-imidazolidine derivatives in search of safer nonsteroidal anti-inflammatory drugs","authors":"Umesh Kumar, Sandhya Bawa, C. Ranjan, G. Chawla","doi":"10.4103/2394-6555.162455","DOIUrl":"https://doi.org/10.4103/2394-6555.162455","url":null,"abstract":"Background: 1,2,3-trisubstituted imidazolidines are reported to have better anti-inflammatory activity than the reference drug indomethacin. Similarly, naphthalene nucleus plays a significant role in the drug design. Nabumetone and naproxen are naphthalene nucleus containing anti-inflammatory drugs available in the market. There are also reports that compounds having two naphthalene rings incorporated with a heterocyclic nucleus have good medicinal value. Based on these reports it was planned to synthesize hybrid compounds containing two naphthalene rings with imidazolidine nucleus. Aim: To obtain potent compounds having anti-inflammatory and analgesic activities with reduced gastrointestinal side effects. Materials and Methods: The reaction scheme includes the reaction between 1-naphthaldehyde with ethylenediamine to obtain diSchiff′s base (1) Reduction of this diSchiff′s base with NaBH 4 gave tetrahydrodiSchiff′s base (2) Further cyclization of 2 with appropriate aldehyde in the presence of ethanol formed 2-substituted-1,3-bis(1-naphthylmethyl)-imidazolidine derivatives (3a-n). The structures of these compounds were established on the basis of spectral data. All these compounds were tested for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation activities. Results and Discussion: The tested compounds (3a-n) showed anti-inflammatory activity ranging between 27.61% and 53.43%. The compound 3h showed the highest activity of 53.43% and 3n showed 53.02% inhibition at 20 mg/kg dose in rats compared with the standard drug indomethacin which showed 61.45% inhibition at the same dose. It was encouraging to note that both the compounds showed reduced ulcerogenic activity (less than half) compared to the standard drug indomethacin.","PeriodicalId":11347,"journal":{"name":"Drug Development and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84163448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}