Showing papers by "Central Drug Research Institute published in 2008"
TL;DR: A review of cyclic compounds from the Baylis-Hillman chemistry covering the literature from 2003 to 2007 can be found in this article, where several reaction strategies leading to these cyclic frameworks are delineated in the figure.
473 citations
TL;DR: This review briefly focuses I/R injury-induced multiple mechanisms of apoptosis, involving key apoptotic regulators and their emerging roles in orchestrating cell death programme and the role of autophagy in modulating cell survival/death during cerebral ischemia.
Abstract: Cerebral ischemia/reperfusion (I/R) injury triggers multiple and distinct but overlapping cell signaling pathways, which may lead to cell survival or cell damage. There is overwhelming evidence to suggest that besides necrosis, apoptosis do contributes significantly to the cell death subsequent to I/R injury. Both extrinsic and intrinsic apoptotic pathways play a vital role, and upon initiation, these pathways recruit downstream apoptotic molecules to execute cell death. Caspases and Bcl-2 family members appear to be crucial in regulating multiple apoptotic cell death pathways initiated during I/R. Similarly, inhibitor of apoptosis family of proteins (IAPs), mitogen-activated protein kinases, and newly identified apoptogenic molecules, like second mitochondrial-activated factor/direct IAP-binding protein with low pI (Smac/Diablo), omi/high-temperature requirement serine protease A2 (Omi/HtrA2), X-linked mammalian inhibitor of apoptosis protein-associated factor 1, and apoptosis-inducing factor, have emerged as potent regulators of cellular apoptotic/antiapoptotic machinery. All instances of cell survival/death mechanisms triggered during I/R are multifaceted and interlinked, which ultimately decide the fate of brain cells. Moreover, apoptotic cross-talk between major subcellular organelles suggests that therapeutic strategies should be optimally directed at multiple targets/mechanisms for better therapeutic outcome. Based on the current knowledge, this review briefly focuses I/R injury-induced multiple mechanisms of apoptosis, involving key apoptotic regulators and their emerging roles in orchestrating cell death programme. In addition, we have also highlighted the role of autophagy in modulating cell survival/death during cerebral ischemia. Furthermore, an attempt has been made to provide an encouraging outlook on emerging therapeutic approaches for cerebral ischemia.
247 citations
TL;DR: A new series of thiophene containing triarylmethane derivatives were synthesized from the Friedel-Crafts alkylation of diarylcarbinols followed by incorporation of amino alkyl chains and showed the activity in the range of 3.12-12.5 microg/mL in vitro.
181 citations
TL;DR: New anti-inflammatory agents possessing dual cyclooxygenase/lipoxygenases (COX/LOX) inhibition were discovered by computer-aided prediction of biological activity for 573 virtually designed chemical compounds.
Abstract: New anti-inflammatory agents possessing dual cyclooxygenase/lipoxygenase (COX/LOX) inhibition were discovered by computer-aided prediction of biological activity for 573 virtually designed chemical compounds. Prediction of biological activity was performed by PASS, and prediction results were analyzed with PharmaExpert software. Nine 2-(thiazole-2-ylamino)-5-phenylidene-4-thiazolidinone derivatives differing by the phenyl group substitution were selected for synthesis and experimental testing as potential COX/LOX inhibitors. Eight tested compounds exhibited anti-inflammatory activity in the carrageenin-induced paw edema. It was shown that seven tested compounds (77.8%) were LOX inhibitors, seven compounds were COX inhibitors (77.8%), and six tested compounds (66.7%) were dual COX/LOX inhibitors. Analysis of lipophilicity of the compounds showed a negative correlation with inhibition of edema formation. The binding modes of the most active compounds of this series (2-(thiazole-2-ylamino)-5-( m-chlorophenylidene)-4-thiazolidinone for COX-1 and COX-2, and 2-(thiazole-2-ylamino)-5-( m-nitrophenylidene)-4-thiazolidinone for 15-LOX) were proposed on the basis of docking studies.
156 citations
TL;DR: The results indicate that fireworks during Diwali festival affected the ambient air quality adversely due to emission and accumulation of PM10, SO2, NOx and trace metals.
Abstract: The present study deals with the effect of fireworks on ambient air quality during Diwali Festival in Lucknow City. In this study, PM10, SO2, NOx and 10 trace metals associated with PM10 were estimated at four representative locations, during day and night times for Pre Diwali (day before Diwali) and Diwali day. On Diwali day 24 h average concentration of PM10, SO2, and NOx was found to be 753.3, 139.1, and 107.3 μg m−3, respectively, and these concentrations were found to be higher at 2.49 and 5.67 times for PM10, 1.95 and 6.59 times for SO2 and 1.79 and 2.69 for NOx, when compared with the respective concentration of Pre Diwali and normal day, respectively. On Diwali day, 24 h values for PM10, SO2, and NOx were found to be higher than prescribed limit of National Ambient Air Quality Standard (NAAQS), and exceptionally high (7.53 times) for PM10. On Diwali night (12 h) mean level of PM10, SO2 and NOx was 1,206.2, 205.4 and 149.0 μg m−3, respectively, which was 4.02, 2.82 and 2.27 times higher than their respective daytime concentrations and showed strong correlations (p Fe (747.23)>Zn (542.62)>Cu (454.03),>Pb (307.54)>Mn (83.90)>Co (78.69)>Cr (42.10)>Ni (41.47)>Cd (34.69) in ng m−3 and all these values were found to be higher than the Pre Diwali (except Fe) and normal day. The metal concentrations on Diwali day were found to be significantly different than normal day (except Fe & Cu). The concentrations of Co, Ni, Cr and Cd on Diwali night were found to be significantly higher than daytime concentrations for Pre Diwali (control). The inter correlation of metals between Ca with Pb, Zn with Ni and Cr, Cu with Co, Co with Mn, Ni with Cd, Mn with Cd, Ni with Cd and Cr, and Cr with Cd showed significant relation either at p<0.05 or P<0.01 levels, which indicated that their sources were the same. The metals Cu, Co, Ni, Cr and Cd showed significant (p<0.01) association with PM10. These results indicate that fireworks during Diwali festival affected the ambient air quality adversely due to emission and accumulation of PM10, SO2, NOx and trace metals.
140 citations
TL;DR: Results indicate that tacrine and donepezil, beside inhibition of acetylcholinesterase, may also suppress oxidative stress.
138 citations
TL;DR: Deciphering the role of macrophages in regulating dyslipidemia and inflammation during atherosclerosis is important for developing them as therapeutic targets.
Abstract: Macrophages are central to the initiation and progression of atherosclerosis and thus can be very appropriate targets for therapy. Cell adhesion molecules mediating monocytes recruitment to the endothelium are attractive therapy targets and their inhibitors are in clinical trials. Macrophage scavenger receptors like SR-A and CD-36 mediate foam cell formation by facilitating the uptake of modified lipids. Peroxisome proliferator-activated receptors (PPAR), liver X receptor (LXR)-mediated signaling, mitogen-activated protein kinase (MAPK) induced phosphorylation events seem to play an important role in this phenomenon. Proteins affecting macrophage cholesterol metabolism and transport, including ATP-binding cassette (ABC) A1, ABCG1, acyl-CoA:cholesterol acyltransferase (ACAT), apolipoprotein A-1 (ApoA-1), neutral cholesteryl ester hydrolase (NCEH) also regulate foam cell formation and are being developed as therapeutic targets by many pharmaceutical companies. Macrophage proliferation and apoptosis are important events controlling inflammatory response, plaque vulnerability, and destabilization. Free cholesterol (FC) activates the macrophage endoplasmic reticulum (ER) stress pathway and apoptosis. Free radicals and nitric oxide also modulate macrophage foam cell formation and apoptosis. Various antioxidants like AGI-1067 and BO-653 are in clinical trials for atherosclerosis treatment. Macrophage matrix metalloproteinase's (MMP's) play a significant role in weakening and rupture of plaques. Efforts are on to develop isoform specific MMP inhibitor. CD-14, MMP-3, ABCA1, Toll-like receptor-4 (TLR-4), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), arachidonate lipoxygenase-15 (ALOX-15), and Connexin37 polymorphisms and macrophage dysfunction signify their importance in atherosclerosis. Deciphering the role of macrophages in regulating dyslipidemia and inflammation during atherosclerosis is important for developing them as therapeutic targets.
138 citations
TL;DR: It is shown that K is non-estrogenic in vivo and exerts bone anabolic activity with attendant inhibition of bone marrow adipogenesis, and exhibits no estrogenicity at the uterine level.
130 citations
TL;DR: Association of specific TNF and FCGR2A SNPs with cytokine levels and disease severity/resistance was indicated in patients from areas with differential disease endemicity, emphasizing the need for addressing the contribution of human genetic factors in malaria in the context of disease epidemiology and population genetic substructure within India.
Abstract: Susceptibility/resistance to Plasmodium falciparum malaria has been correlated with polymorphisms in more than 30 human genes with most association analyses having been carried out on patients from Africa and south-east Asia. The aim of this study was to examine the possible contribution of genetic variants in the TNF and FCGR2A genes in determining severity/resistance to P. falciparum malaria in Indian subjects. Allelic frequency distribution in populations across India was first determined by typing genetic variants of the TNF enhancer and the FCGR2A G/A SNP in 1871 individuals from 55 populations. Genotyping was carried out by DNA sequencing, single base extension (SNaPshot), and DNA mass array (Sequenom). Plasma TNF was determined by ELISA. Comparison of datasets was carried out by Kruskal-Wallis and Mann-Whitney tests. Haplotypes and LD plots were generated by PHASE and Haploview, respectively. Odds ratio (OR) for risk assessment was calculated using EpiInfo™ version 3.4. A novel single nucleotide polymorphism (SNP) at position -76 was identified in the TNF enhancer along with other reported variants. Five TNF enhancer SNPs and the FCGR2A R131H (G/A) SNP were analyzed for association with severity of P. falciparum malaria in a malaria-endemic and a non-endemic region of India in a case-control study with ethnically-matched controls enrolled from both regions. TNF -1031C and -863A alleles as well as homozygotes for the TNF enhancer haplotype CACGG (-1031T>C, -863C>A, -857C>T, -308G>A, -238G>A) correlated with enhanced plasma TNF levels in both patients and controls. Significantly higher TNF levels were observed in patients with severe malaria. Minor alleles of -1031 and -863 SNPs were associated with increased susceptibility to severe malaria. The high-affinity IgG2 binding FcγRIIa AA (131H) genotype was significantly associated with protection from disease manifestation, with stronger association observed in the malaria non-endemic region. These results represent the first genetic analysis of the two immune regulatory molecules in the context of P. falciparum severity/resistance in the Indian population. Association of specific TNF and FCGR2A SNPs with cytokine levels and disease severity/resistance was indicated in patients from areas with differential disease endemicity. The data emphasizes the need for addressing the contribution of human genetic factors in malaria in the context of disease epidemiology and population genetic substructure within India.
96 citations
TL;DR: Docking studies revealed that hydrophobic interactions and hydrogen bond formation stabilize enzyme-inhibitor complex, and Benzo[d]thiazole derivatives exhibited the best inhibitory action.
Abstract: SHP-2, a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene, mediates cell signaling by growth factors and cytokines via the RAS/MAP kinase pathway Somatic mutations in PTPN11 gene account for approximately 18% of juvenile myelomonocytic leukemia (JMML) patients Moreover, SHP-2 mutations leading to continuously active enzyme were found in more than 50% of Noonan syndrome patients and are considered to be responsible for the high tendency of these patients to juvenile leukemias and other cancer types Recently SHP-2 became a new drug target, but till now little has been done in this field In the present study, 17 2-thiazolylimino/heteroarylimino-5-arylidene-4-thiazolidinones divided into three series of derivatives bearing thiazole-, benzo[d]thiazole-, and benzo[d]isothizole rings were tested for SHP-2 inhibitory activity Most of the compounds were good SHP-2 inhibitors Benzo[d]thiazole derivatives exhibited the best inhibitory action Docking studies revealed that hydrophobic interactions and hydrogen bond formation stabilize enzyme-inhibitor complex
92 citations
TL;DR: The increased incidence of fungal infections in the recent past has been attributed to the increase in the number of human immunodeficiency virus‐positive and AIDS patients, and early diagnosis of mycoses in patients is crucial for prompt antifungal therapy.
Abstract: The increased incidence of fungal infections in the recent past has been attributed to the increase in the number of human immunodeficiency virus-positive and AIDS patients. Early diagnosis of mycoses in patients is crucial for prompt antifungal therapy. The yield of clinical examination in the diagnosis of keratomycosis is 63-83% and KOH mount is 91%. This still highlights the limitation of routine clinical examination and smear examination, which is not performing 100% efficiently. It is for these 37%, 17% and 9% of cases, every day advanced technologies are called for. Those who deal with patient care are aware of certainties and uncertainties of results of clinical examination. The best reported figures at specialized centres might not translate into clinical practice. Another factor to be kept in mind is that many patients who come after secondary and tertiary referrals are already treated with antibiotics, antivirals, steroids and sometimes even antifungals that distort the clinical picture completely. Further, one has to consider as well the cases caused by yeast-like fungi, which resemble bacterial keratitis. Confirmation of diagnosis, not only in case of mycotic keratitis but also for other diseases, to initiate prompt and accurate therapy would avoid unnecessary and indiscriminate use of steroids/antibacterials/antivirals and antifungals.
TL;DR: A series of 2,6-dibromophenyl)-3-heteroaryl-1,3-thiazolidin-4-ones were designed, synthesized and evaluated as selective human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) enzyme inhibitors and showed that eight compounds effectively inhibited HIV-1 replication at 20-320 nM concentrations with minimal cytotoxicity in MT-4 as well as in CEM cells.
TL;DR: The synthesized sugar triazoles were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv, where one of the compounds displayed mild antitubcular activity in vitro with MIC 12.5 microg/mL.
TL;DR: It was concluded that inhaled microparticles can reduce dose frequency and improve the pharmacologic index of the drug combination.
Abstract: Intracellular concentrations of isoniazid and rifabutin resulting from administration of inhalable microparticles of these drugs to phorbol-differentiated THP-1 cells and the pharmacokinetics and biodistribution of these drugs upon inhalation of microparticles or intravenous administration of free drugs to mice were investigated. In cultured cells, both microparticles and dissolved drugs established peak concentrations of isoniazid ( approximately 1.4 and 1.1 microg/10(6) cells) and rifabutin ( approximately 2 microg/ml and approximately 1.4 microg/10(6) cells) within 10 min. Microparticles maintained the intracellular concentration of isoniazid for 24 h and rifabutin for 96 h, whereas dissolved drugs did not. The following pharmacokinetic parameters were calculated using WinNonlin from samples obtained after inhalation using an in-house apparatus (figures in parentheses refer to parameters obtained after intravenous administration of an equivalent amount, i.e., 100 microg of either drug, to parallel groups): isoniazid, serum half-life (t(1/2)) = 18.63 +/- 5.89 h (3.91 +/- 1.06 h), maximum concentration in serum (C(max)) = 2.37 +/- 0.23 microg x ml(-1) (3.24 +/- 0.57 microg x ml(-1)), area under the concentration-time curve from 0 to 24 h (AUC(0-24)) = 55.34 +/- 13.72 microg/ml(-1) h(-1) (16.64 +/- 1.80 microg/ml(-1) h(-1)), and clearance (CL) = 63.90 +/- 13.32 ml x h(-1) (4.43 +/- 1.85 ml x h(-1)); rifabutin, t(1/2) = 119.49 +/- 29.62 h (20.18 +/- 4.02 h), C(max) = 1.59 +/- 0.01 microg x ml(-1) (3.47 +/- 0.33 microg x ml(-1)), AUC(0-96) = 109.35 +/- 14.78 microg/ml(-1) h(-1) (90.82 +/- 7.46 microg/ml(-1) h(-1)), and CL = 11.68 +/- 7.00 ml x h(-1) (1.03 +/- 0.11 ml.h(-1)). Drug targeting to the lungs in general and alveolar macrophages in particular was observed. It was concluded that inhaled microparticles can reduce dose frequency and improve the pharmacologic index of the drug combination.
TL;DR: The present investigation demonstrates the hepatoprotective potential of 50% ethanolic water extract of whole plant of Fumaria indica and its three fractions viz., hexane, chloroform and butanol against d-galactosamine induced hepatotoxicity in rats.
TL;DR: It was observed that lipid peroxidation started to increase and catalase, glutathione reductase, glucose-6-phosphate dehydrogenase enzyme activities and glutATHione levels started to decrease as amyotrophic lateral sclerosis progressed from 6 to 24 months, suggesting a correlation between these parameters and duration of amyotroph lateral sclerosis.
TL;DR: First evidence of effectiveness of curcumin when given 4h post-ischemia in the rat thromboembolic stroke models is shown, as it reduces infarct volume, ameliorates the sensory motor function and significantly attenuated the nitrosative stress.
TL;DR: In this article, a bilateral intracerebroventricular (ICV) administration of Lipopolysaccharide (LPS) was shown to induce neuroinflammation in different brain regions at different time points after LPS injection.
TL;DR: A series of new class of hybrid 4-aminoquinoline triazines were synthesized and screened against CQ sensitive strain 3D7 of Plasmodium falciparum in an in vitro model and exhibited impressive suppression levels.
TL;DR: The involvement of inflammation in ALS is confirmed and the need to develop surrogate markers to check the progression of this disease is confirmed.
Abstract: The role of cytokines in the pathophysiology of amyotrophic lateral sclerosis (ALS) and its relation to clinical outcome has not been clearly defined. We evaluated tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ) and nitric oxide (NO) levels in the serum of 22 ALS patients and 20 controls. Serum TNF-α levels and IFN-γ levels were significantly (P < 0.001) elevated in ALS patients. We also observed NO levels to be significantly (P < 0.05) increased with respect to normal subjects. We further noticed positive correlation between the duration of ALS and these proinflammatory molecule levels. Exitotoxicity and oxidative stress are known to play a crucial role in the neurodegeneration observed in ALS. Since high levels of TNF-α are known to be cytotoxic, it could be that a complex interplay of these effectors may be one of the factors underlying the progression of ALS. This study confirms the involvement of inflammation in ALS and the need to develop surrogate markers to check the progression of this disease.
TL;DR: The study suggests that the reduced CAG repeats in the AR gene are associated with criminal behavior, which would help in understanding the biological factors associated with the antisocial or criminal activities.
Abstract: Androgens mediate their functions through androgen receptors (AR) The two triplet repeats in the AR gene (CAG and GGN) are highly polymorphic among various populations and have been extensively studied in diverse clinical conditions and antisocial personality disorders Several studies have reported either higher levels of testosterone among rapists or the correlation of shorter CAG repeats with criminal activities However, to date, no study has analyzed AR gene in rapists worldwide, and no study has been conducted on criminals from Indian subcontinent Therefore, we have analyzed the AR-CAG repeat length in 645 men, of which 241 were convicted for rape, 107 for murder, 26 for both murder and rape, and 271 were control males The aim was to explore if there was any correlation between CAG repeat length and criminal behavior The study revealed significantly shorter CAG repeats in the rapists (mean 1844 repeats) and murderers (mean 1759 repeats) compared to the control men (mean 2119 repeats) The criminals who committed murder after rape had a far shorter mean repeat length (mean 1731 repeats) in comparison to the controls or those convicted of rape or murder alone In short, our study suggests that the reduced CAG repeats in the AR gene are associated with criminal behavior This, along with other studies, would help in understanding the biological factors associated with the antisocial or criminal activities
TL;DR: The results suggest that the neuroprotective activity of C.oil against cerebral ischemia is associated with its antioxidant activities and further; there is attenuation of delayed neuronal death via a caspase-dependent pathway.
Abstract: Turmeric is a source of numerous aromatic compounds isolated from powdered rhizomes of Curcuma longa Linn. The constituents are present as volatile oil, the Curcuma oil (C.oil), semi-solid oleoresins and non-volatile compounds such as curcumin. A rapidly expanding body of data provides evidence of the anti-cancer action of Curcumin, and most importantly in the present context, its neuroprotective activity. Almost nothing is known about such activity of C.oil. We report that C.oil (500 mg Kg(-1) i.p.) 15 min before 2 h middle cerebral artery occlusion (MCAo) followed by 24 h reflow in rats significantly diminished infarct volume, improved neurological deficit and counteracted oxidative stress. The percent ischemic lesion volume on diffusion-weighted imaging was significantly attenuated. Mitochondrial membrane potential, reactive oxygen species, peroxynitrite levels, caspase-3 activities leading to delayed neuronal death were significantly inhibited after treatment with C.oil. These results suggest that the neuroprotective activity of C.oil against cerebral ischemia is associated with its antioxidant activities and further; there is attenuation of delayed neuronal death via a caspase-dependent pathway. C.oil appears to be a promising agent not only for the treatment of cerebral stroke, but also for the treatment of other disorders associated with oxidative stress.
TL;DR: Early response of saponins to disrupt actin cytoskeleton in comparison with their effect on the nucleus suggests a membrane-mediated mode of action rather than via induction of apoptosis, demonstrating the potential of Sapindus sap onins for development as a microbicidal contraceptive for human use.
Abstract: Objectives: Trichomoniasis is the most common non-viral sexually transmitted disease and is caused by the protozoan Trichomonas vaginalis. In view of increased resistance of the parasite to classical drugs of the metronidazole family, the need for new unrelated agents is increasing. This study evaluates anti-Trichomonas activity of Sapindus saponins, a component of a herbal local contraceptive Consap recently marketed in India. Methods: The parasites were treated with saponins for MIC determination. Anti-Trichomonas activity of the saponins was evaluated using a cytoadherence assay, the substrate gel electrophoresis method and RT-PCR analysis. The effect of saponins on the mitochondrial potential of the host was determined by florescence-activated cell sorter. Actin cytoskeletal staining was used to determine the effect on parasite cytoskeleton. Results: Using in vitro susceptibility assay, the MIC of Sapindus saponins for T. vaginalis (0.005%) was found to be 10-fold lower than its effective spermicidal concentration (0.05%). Saponins concentration dependently inhibited the ability of parasites to adhere to HeLa cells and decreased proteolytic activity of the parasite's cysteine proteinases. This was associated with decreased expression of adhesin AP65 and membrane-expressed cysteine proteinase TvCP2 genes. Saponins produced no adverse effect on host cells in mitochondrial reduction potential measurement assay. Saponins also reversed the inhibitory mechanisms exerted by Trichomonas for evading host immunity. Early response of saponins to disrupt actin cytoskeleton in comparison with their effect on the nucleus suggests a membrane-mediated mode of action rather than via induction of apoptosis. Conclusions: Findings demonstrate the potential of Sapindus saponins for development as a microbicidal contraceptive for human use. Further studies are required to evaluate its microbicidal activity against other sexually transmitted infections.
TL;DR: It is demonstrated that iNOS-derived NO produced during ischemia injury was crucial for the up-regulation of ischemic injury targets and down-regulates these targets this coincided with an increased survival rate of neurons.
Abstract: Among the naturally occurring compounds, turmeric from the dried rhizome of the plant Curcuma longa has long been used extensively as a condiment and a household remedy all over Southeast Asia. Turmeric contains essential oil, yellow pigments (curcuminoids), starch and oleoresin. The present study was designed for investigating the neuroprotective efficacy and the time window for effective therapeutic use of Curcuma oil (C. oil). In the present study, the effect of post ischemic treatment of C.oil after ischemia induced by occlusion of the middle cerebral artery in the rat was observed. C.oil (500 mg/kg body wt) was given 4 hrs post ischemia. The significant effect on lesion size as visualized by using diffusion-weighted magnetic resonance imaging and neuroscore was still evident when treatment was started 4 hours after insult. Animals were assessed for behavioral deficit scores after 5 and 24 hours of ischemia. Subsequently, the rats were sacrificed for evaluation of infarct and edema volumes and other parameters. C.oil ameliorated the ischemia induced neurological functional deficits and the infarct and edema volumes measured after 5 and 24 hrs of ischemia. After 24 hrs, immunohistochemical and Western blot analysis demonstrated that the expression of iNOS, cytochrome c and Bax/Bcl-2 were altered after the insult, and antagonized by treatment with C.oil. C.oil significantly reduced nitrosative stress, tended to correct the decreased mitochondrial membrane potential, and also affected caspase-3 activation finally apoptosis. Here we demonstrated that iNOS-derived NO produced during ischemic injury was crucial for the up-regulation of ischemic injury targets. C.oil down-regulates these targets this coincided with an increased survival rate of neurons.
TL;DR: Results showed that pongamol and karangin isolated from the fruits of Pongamia pinnata possesses significant antihyperglycemic activity in Streptozotocin-induced diabetic rats and type 2 diabetic db/db mice and protein tyrosine phosphatase-1B may be the possible target for their activity.
TL;DR: A series of hybrid molecules 2-[3-(7-Chloro-quinolin-4-ylamino)-alkyl]-1-(substituted phenyl)-2,3,4,9-tetrahydro-1H-beta-carbolines have been synthesized and screened for their in vitro antimalarial activity against chloroquine-sensitive strains of Plasmodium falciparum.
TL;DR: Findings have revealed that collagen receptor inhibition is an attractive and secure strategy for the new drug development to prevent intravascular thrombosis.
TL;DR: Nano-amphotericin B, a nano form of amphotericin B deoxycholate formulated by applying high-pressure (150 argon) milling homogenization, had significantly greater efficacy than conventional amphoteric in B for the treatment of visceral leishmaniasis.
Abstract: Objectives: The aim of the present study was to compare the efficacy of a nano form of amphotericin B deoxycholate with that of conventional amphotericin B deoxycholate for the treatment of visceral leishmaniasis. Methods: We have formulated nanoparticles (10‐20 nM) from amphotericin B deoxycholate (1‐2 mM) by applying high-pressure (150 argon) milling homogenization and have tested their efficacy in a J774A cell line and in hamsters. Parasite survival and tissue burden in spleen were evaluated for nanoamphotericin B and conventional amphotericin B. Both nano-amphotericin B and conventional amphotericin B were injected intraperitoneally at 5 mg/kg per day for 5 days. Results: The inhibition of amastigotes in the splenic tissue with nano-amphotericin B was significantly more than with conventional amphotericin B (92.18% versus 74.57%, P 5 0.005). Similarly, the suppression of parasite replication in the spleen was also found to be significant (99.18% versus 97.17%, P 5 0.05). In a cytotoxicity test, nano-amphotericin B against the J774A cell line had a CC50 of 12.67 mg/L in comparison with 10.61 mg/L for amphotericin B, far higher than the doses used for ED50. Conclusions: Nanoparticles of amphotericin B had significantly greater efficacy than conventional amphotericin B. This formulation may have a favourable safety profile, and if production costs are low, it may prove to be a feasible alternative to conventional amphotericin B.
TL;DR: The results provide further support to explain the traditional use of W. coagulans as antihyperglycemic cum antidyslipidemic agent by the traditional medical practitioners.
TL;DR: Results demonstrate that CC induces caspase-dependent apoptosis in MCF-7 and MDA MB-231 cells irrespective of ER status similar to TAM in terms of anti-neoplastic activity.