Insignificant anticancer activity of novel substituted pyrimidine derivatives

Anshu Chaudhary, Pramod Kumar Sharma, Shiv Jee Kashyap, Jitendra Kumar Gupta, Rupesh Dudhe, Prabhakar Verma

Journal of Pharmaceutical Negative Results 2011 2(2):62-68

Background: Pyrimidine and fused pyrimidine derivatives play an important role in therapeutic strategies. It is known to be most prominent structures found in nucleic acid, including uracil, thymine, cytosine, adenine, and guanine, which are fundamental building blocks for deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Materials and Methods: A series of 3-[2-amino-6-(substituted)-pyrimidin-4-yl]-6-(substituted)-2H-chromen-2-one derivatives were prepared by reacting salicylaldehyde with ethylacetoacetate in the presence of piperidine by Knoevenagel reaction as a starting material. The chemical structures were confirmed by means of FTIR (Fourier Transform InfraRed Spectrophotometer-8400S), 1H NMR, and elemental analysis. The data of these synthesized compounds were submitted to National Institute of Health, USA, under the drug discovery program of NCI (National Cancer Institute) and screened for anticancer activity at a single high dose (10−5 M) in full NCI 60 cell lines. Results: Unfortunately, the selected compounds have not shown any potent significant anticancer activity in the NCI 60 cell line screening. Conclusion: The compound (T2) found to be most efficient anticancer activity with selective influence on breast cancer cell lines, especially on MCF7 cell line with a growth percentage of 33.63.

Ultra violet spectrophotometric method: Not possible for the simultaneous estimation of alpha one adrenoreceptor blockers

Alankar Shrivastava, Vipin Bihari Gupta

Journal of Pharmaceutical Negative Results 2011 2(2):115-120

Background: Although initially introduced for the management of hypertension, al-adrenergic-receptor antagonists (a 1 blockers) have become the standard of care for the medical management of benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS). Alpha-blockers (alfuzosin, tamsulosin, doxazosin, prazosin, and terazosin) relax the smooth muscles in the prostate and are indicated for the symptomatic treatment of BPH, due to evidence of their positive and rapid effect on LUTS. Objective: Our objective was to develop and validate a method for simultaneous estimation of these drugs. Our aim was to develop a UV spectrophotometric method because of the simplicity and economical advantage of this technique. Materials and Methods: All these drugs were dissolved in the same solvent (methanol) and scanned under a ShimadzuUV spectrophotomer, under full UV (ultraviolet) range (200 – 400 nm). Result: After some experiments we found that this is impossible. This was evident from our study that UV spectra were overlapping each other, except in the case of tamsulosin. Conclusion: Same class of drugs may have almost the same functional groups, and gradient Reverse-Phase Liquid Chromatography(RPLC) will be more useful to separate such complicated mixtures. Therefore, we propose to develop a gradient High-Performance Liquid Chromatography(HPLC) method as it may be a more suitable method for the simultaneous estimation of these drugs.

Hydroethanolic leaf extract of Ficus religiosa lacks anticonvulsant activity in acute electro and chemo convulsion mice models

Damanpreet Singh, Bikram Singh, Rajesh Kumar Goel

Journal of Pharmaceutical Negative Results 2011 2(2):58-61

Introduction: Ficus religiosa L. (Moraceae) has been of great medicinal value in traditional medicine and implicated in a wide variety of human and animal disorders. Its leaves have been used for the ethnomedical treatment of epilepsy. But its traditional antiepileptic use is not fully understood experimentally. Hence the present study was undertaken to explore the anticonvulsant effect of the leaves in experimental animal models of convulsion. Materials and Methods: The anticonvulsant effect of hydroethanolic leaf extract of F. religiosa was studied at 100, 250 and 500 mg/kg; intraperitoneally (i.p.) in maximal electroshock (MES), and at 100, 250, 500 and 600 mg/kg; i.p. doses in pentylenetetrazol (PTZ) test in mice. The duration of tonic hind limb extension(s) and latency to clonic convulsions (min) was noted in MES and PTZ tests, respectively. Phenytoin (25 mg/kg; i.p.) and diazepam (5 mg/kg; i.p.) served as reference standards in MES and PTZ tests, respectively. Percentage mortality was also noted. Results: There was no significant change observed after the extract treatment on the duration of tonic hind limb extension in MES test, and latency to clonic convulsions in PTZ test, as compared to their respective controls. Moreover, percentage mortality remained unaltered after the extract treatment. Conclusions: From the results of present study it is concluded that the hydroethanolic leaf extract of F. religiosa lacks anticonvulsant activity in MES- and PTZ-induced convulsion tests. Further studies are required from other regions and using different animal models to support these findings.

A comparative study of pheniramine and lorazepam for physiological and cognitive/psychomotor task impairment

Yatan Pal Singh Balhara, Raka Jain, Anju Dhawan, Manju Mehta

Journal of Pharmaceutical Negative Results 2011 2(2):91-98

Context: Pheniramine is being used harmfully in combination with opiates and benzodiazepines through injecting route. Aims: The present study is an attempt to compare the physiological and psychomotor/cognitive task performance on pheniramine and lorazepam. Settings and Design: The study used a double blind randomly allotted cross-over design. Materials and Methods: The doses of the drugs used were placebo (normal saline) – 2 ml, Pheniramine maleate – 45.5 mg, Lorazepam – 2 mg. The assessments were made at base line and then at 15 min., 120 min and 240 min. The subjects were assessed for the socio-demographic profile, drug use history, physiological parameters (pulse rate, BP, respiratory rate), and psychomotor/cognitive tasks. Statistical Analysis used : Analysis was carried out using SPSS ver 10.0. In between, drug comparisons were done using one-way ANOVA (multiple comparisons). Results: Physiological and cognitive/psychomotor tasks performance did not show any significant difference between pheniramine, lorazepam and placebo. Conclusions: The findings suggest the pheniramine and lorazepam have comparable impairment on physiological and cognitive/psychomotor task performance.

Lack of antiglycation activity of fresh juice of whole plant of Enicostema axillare (Lam.) Raynal

WD Ratnasooriya, K.I.W.K Somarathna, G.A.S Premakumara, E.R.H.S.S Ediriweera

Journal of Pharmaceutical Negative Results 2011 2(2):55-57

Objective: To investigate the antiglycation potential of fresh juice of whole plant of Enicostema axillare (Lam.) Raynal. in vitro. Materials and Methods: Antiglycation activity of fresh juice of whole plant was determined in vitro using five concentrations (25, 50, 100, 200, and 400 μg/ml) by determining their ability to inhibit the formation of advanced glycation endproducts in a bovine serum albumin / glucose system using fluorescence spectroscopy. Results: There is no antiglycation activity in vitro of fresh juice of E. axillare plant. Conclusion: It is unlikely that impairment of diabetic complications by E. axillare whole plant juice as claimed by ayurvedic and traditional physicians is mediated via antiglycation activity.

Absence of antimicrobial activity in alcoholic extract of Santalum album Linn

Vaishali Patil, GP Vadnere, Neeraj Patel

Journal of Pharmaceutical Negative Results 2011 2(2):107-109

Objective: The objective of the present study was to investigate the antimicrobial activity of seed of Santalum album Linn. (Family: Santalaceae) in various microbial strains. Materials and Methods: The effects of ethanolic extract of seed of S. album were analyzed in different microorganisms at a concentration of 5 mg/ml per disk. Results: The result indicated that the ethanolic extract of seed of S. album did not show any zone of inhibition against the tested microorganisms. Conclusion: The ethanolic extract of seed of S. album has no significant antimicrobial activity.

Anticonvulsant activity of Passiflora incarnata: No role of chrysin

Bhupinder Singh, Awanish Mishra, Rajesh Kumar Goel

Journal of Pharmaceutical Negative Results 2011 2(2):51-54

The earlier studies on Passiflora incarnata have pointed out the possible role of chrysin for its anticonvulsant activity. But role of chrysin in anticonvulsant property of P. incarnate seems to be controversial due to its poor bioavailability reported by different studies. Therefore, this study was designed to investigate the role of chrysin in anticonvulsant property of different extracts of P. incarnata used for medicinal purpose, viz. aqueous (PIAE), hydroethanolic (PIHE), and methanolic extracts (PIME). These extracts were prepared from dried leaves of P. incarnata using water, methanol, and 50% ethanol to obtain PIAE, PIME, and PIHE, respectively. The extracts were standardized with reference to chrysin by HPLC-UV method. Different doses (150, 300 and 600 mg/kg; i.p.) of PIAE, PIME, PIHE, and chrysin (1 mg/kg) were administered 30 min before the PTZ injection (75 mg/kg) to evaluate anticonvulsant effect. HPLC estimation has shown the higher amount of chrysin present in PIME followed by PIAE and PIHE. Significant dose-dependent delay in onset of convulsions was observed in PIHE and PIAE treated mice when compared with PTZ convulsive mice, while PIME treatment has not shown delay in onset of convulsions. Chrysin (1 mg/kg, i.p.), as well, did not produce significant increment in onset of convulsions. These results revealed that PIME containing significant amount of chrysin lacks anticonvulsant effect, while PIAE and PIHE, with insignificant chrysin content, have shown significant anticonvulsant effect. Thus, this study suggests that chrysin is not responsible for anticonvulsant effect of P. incarnata.

Rimonabant: Boom to ban

Suyog S Jain, Vitthal B Karande, Karuna B Ramteke, Girish T Raparti

Journal of Pharmaceutical Negative Results 2011 2(2):45-50

Rapidly rising prevalence of obesity and health care cost of its complications necessities need for highly efficacious and safe antiobesity drugs. As most old antiobesity drugs had moderate efficacy, severe toxicity and some of them very costly. Rimonabant, CB1 receptor antagonist was introduced with high expectations. Rimonabant has multiple beneficial effects, apart from significant weight loss it increases HDL and reduces triglycerides, Hb A 1C level, prevalence of metabolic syndrome. This wide spectrum of effects helps in comprehensive management of obesity and associated complications. Cost of rimonabant (generic Rs.5-8 per tablet) is also much lesser than the only other commonly used antiobesity drug orlistat around Rs. 40 per tablet. During trials rimonabant apart from nausea had neuropsychiatric side effects. EMEA approved rimonabant in June 2006 with concern over its psychiatric side effects. In 2007 EMEA contraindicated rimonabant in patients of depression or taking antidepressants. Further analysis in 2008 concluded that the incidence of psychiatric side effects was higher in clinical practice compared to controlled trials also few cases of suicide became a major safety concern, finally leading to suspension of its sale by EMEA in Oct 2008. USFDA never approved rimonabant over safety concerns, while India banned it shortly thereafter as precautionary measure. Present paper deals with the various events during the rapid rise and fall of rimonabant which was widely considered as blockbuster diet pill but was suspended over serious neuropsychiatric side effects.

Hypoglycemic and in Vitro Antioxidant Effects of Methanolic extract of Marsilea quadrifolia Plant

Phyto-Pharmacognostical Studies of two endangered species of Malaxis (Jeevak and Rishibhak)

Pharmacognostic and Phytochemical Evaluation of Citrus aurantifolia (Christm) Swingle PEEL

Phytochemical Investigation of Methanolic Extract of Cassia fistula Leaves

Phytochemical Screening and in vitro Antioxidant Activity of Jawarish Amla- A Poly Herbal Formulation

Pharmacognostic Evaluation of Cordia macleodii Hook. Stem Bark

Development of Fingerprinting Methods of Balacaturbhadrika Churna: An Ayurvedic Formulation

Determination of Phyllanthin and Gallic Acid In Herbal Hepatoprotective Formulation By TLC-Densitometry Analysis

Pharmacognostical Standardization of Tephrosia maxima Pers Root

Pharmacognostic Standardization and Phytochemical screening of Leaves of Amaranthus spinosus L.

Development of Quality Standards of Terminalia catappa Leaves

Phytochemical analysis and antioxidant activity of Alstonia scholaris

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