Molecular docking analysis of vascular endothelial growth factor receptor with bioactive molecules from Piper longum as potential anti-cancer agents.
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ABSTRACT:
SUBMITTER: Jayaraman S
PROVIDER: S-EPMC8340711 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Piper longum (Indian long pepper) is known for its use as an anti inflammatory agent in Indian Ayurvedic System of medicine. Therefore, it is of interest to document the molecular docking analysis of compounds from Piper longum with COX-2 using the Autodock Vina PyRx tool. Molecular docking results show that asarinine, sesamine, fargesin, and piperlonguminine have optimal binding energy of 10, 10, -9.5 and 9.4 Kcal/mol, respectively for further consideration.
| S-EPMC8819790 | biostudies-literature
Project description:Angiogenesis refers to the formation of new blood vessels, controlled by certain chemicals, which on stimulation repairs damaged cells or form new ones. Other chemicals, called angiogenesis inhibitors, signal the process to stop, having only mild side effects and are non toxic to most healthy cells. In our study, attempt was made to find potent anti-angiogenic inhibitor (pazopanib was considered as a reference drug) for vascular endothelial growth factor receptor (VEGFR-1/FLT-1), which served as a molecular target, using natural agents targeting biological processes important in cancer. Hundreds of natural molecules were initially screened based on lipinski's rule of five and the satisfying ones were taken for receptor-ligand interaction study using docking tools like HEX and quantum. Around fifteen molecules were taken as lead molecule and their binding pocket on VEGF was analyzed using SwissPDBviewer and Q-site finder. The investigational drug pazopanib was found to be interacting with leucine 32 and glutamine 30 in terms of hydrogen bond with the distance of 1.86 and 2.49 A0 respectively. Ames test for the molecules was predicted for probability of mutagenicity on molecular systems such as blood, cardiovascular system, gastrointestinal system; kidney, liver and lung were considered for further screening of the molecules. The natural molecules curcumin, epigallocatechin gallate (EGCG), barrigtozenol and finasteride were showing reliable interaction with VEGFR and their pharmacokinetics parameters were comparatively good than the pazopanib. The dietary product curcumin and EGCG can be cancer chemopreventive agents and the natural molecules barringtozenol and finasteride can be effective inhibitors for VEGFR.
| S-EPMC3532009 | biostudies-literature
Project description:PurposeTo study the prevalence of sustained intraocular pressure (IOP) elevation associated with intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents.MethodsProspective comparative study. Non-glaucomatous patients scheduled to receive intravitreal injection of anti-VEGF therapy were recruited from an outpatient eye clinic, Songklanagarind Hospital between April 2013 and March 2014. The IOP was measured by Goldmann applanation tonometer before and at 1 hour, 1 week, 1 month, 3 months, and 6 months after injection. The IOP was compared using the repeated measures analysis. Sustained IOP elevation was defined as either an IOP > 21 mmHg or an increase from baseline ≥ 5 mmHg on two consecutive visits.ResultsSeventy eyes of 54 patients met the inclusion criteria. The most common diagnosis was diabetic macular edema (48%). The mean IOP ± standard deviation (SD) before treatment was 13.7 ± 2.8 mmHg. The means ± SDs after treatment at 1 hour, 1 week, 1 month, 3 months, and 6 months were 11.3 ± 2.6, 13.7 ± 3.6, 14.1 ± 3.3, 14.0 ± 2.3, and 13.7 ± 2.4 mmHg, respectively. A mean of IOP difference at 1 hour postinjection and at baseline was -2.36 ± 2.5 mmHg (P < 0.001). Four of 70 treated eyes (5.7%) developed sustained IOP elevation (IOP ≥ 5 mmHg from baseline on two consecutive visits). The IOP returned to baseline levels after 1 month, in three eyes. One eye had sustained IOP elevation at 3 and 6 months follow-up. Thereafter, IOP returned to baseline level. There was no need of anti-glaucoma medication.ConclusionsAfter receiving intravitreal injection of anti-VEGF agent, a small proportion of non-glaucomatous eyes developed a sustained IOP elevation without requiring IOP-lowering treatment. At 1 hour postinjection, there was a significant reduction of the mean IOP compared with the baseline level.
| S-EPMC4567346 | biostudies-literature
Project description:The present study investigated the antioxidant, antibacterial, antiviral and anti-inflammatory activities of different aerial parts (flowers, leaves and seeds) of Datura stramonium. The plant material was extracted with 80% methanol for about 24 h. The sensitivity to microorganisms analysis was performed by the microdilution technique. Antioxidant tests were performed by scavenging the DPPH and ABTS radicals, and by FRAP assay. Anti-inflammatory activity was evaluated through the inhibition of nitric oxide production in activated macrophage RAW 264.7 cells. Cell viability was assessed with an MTT assay. Results show that the flower extract revealed a powerful antimicrobial capacity against Gram-positive bacteria and strong antioxidant and anti-inflammatory activities. No significant cytotoxicity to activated macrophages was recorded. High resolution electrospray ionization mass spectrometry and nuclear magnetic resonance analysis identified two molecules with important anti-inflammatory effects: 12α-hydroxydaturametelin B and daturametelin B. Molecular docking analysis with both pro-inflammatory agents tumor necrosis factor alpha and interleukin-6 revealed that both compounds showed good binding features with the selected target proteins. Our results suggest that D. stramonium flower is a promising source of compounds with potential antioxidant, antibacterial, and anti-inflammatory activities. Isolated withanolide steroidal lactones from D. stramonium flower extract with promising anti-inflammatory activity have therapeutic potential against inflammatory disorders.
| S-EPMC10343631 | biostudies-literature
Project description:This is a phase 3, randomized, double-blind, placebo-controlled multi-center study evaluating the efficacy of pegfilgrastim to reduce the incidence of febrile neutropenia (FN) in patients with newly diagnosed, locally-advanced or metastatic colorectal cancer receiving first-line treatment with bevacizumab and either 5-fluorouracil, Oxaliplatin, Leucovorin (FOLFOX) or 5-fluorouracil, Irinotecan, Leucovorin (FOLFIRI).
This study will also investigate the effect of adding pegfilgrastim to bevacizumab and either FOLFOX or FOLFIRI by evaluating overall survival, progression-free survival, and overall response rate in each arm at regular intervals over a maximum of 60 months follow-up.
| 2073020 | ecrin-mdr-crc
Project description:Treatment of glioblastoma (GBM), the most common primary malignant brain tumor in adults, remains a significant unmet need in oncology. Historically, cytotoxic treatments provided little durable benefit, and tumors recurred within several months. This has spurred a substantial research effort to establish more effective therapies for both newly diagnosed and recurrent GBM. In this context, antiangiogenic therapy emerged as a promising treatment strategy because GBMs are highly vascular tumors. In particular, GBMs overexpress vascular endothelial growth factor (VEGF), a proangiogenic cytokine. Indeed, many studies have demonstrated promising radiographic response rates, delayed tumor progression, and a relatively safe profile for anti-VEGF agents. However, randomized phase III trials conducted to date have failed to show an overall survival benefit for antiangiogenic agents alone or in combination with chemoradiotherapy. These results indicate that antiangiogenic agents may not be beneficial in unselected populations of patients with GBM. Unfortunately, biomarker development has lagged behind in the process of drug development, and no validated biomarker exists for patient stratification. However, hypothesis-generating data from phase II trials that reveal an association between increased perfusion and/or oxygenation (ie, consequences of vascular normalization) and survival suggest that early imaging biomarkers could help identify the subset of patients who most likely will benefit from anti-VEGF agents. In this article, we discuss the lessons learned from the trials conducted to date and how we could potentially use recent advances in GBM biology and imaging to improve outcomes of patients with GBM who receive antiangiogenic therapy.
| S-EPMC4517055 | biostudies-literature
Project description:The aim of this study was to evaluate the efficacy and tolerability of photodynamic therapy (PDT) compared to intravitreal vascular endothelial growth factor (VEGF) inhibitors in the treatment of polypoidal choroidal vasculopathy (PCV).Relevant studies were selected through an extensive search of the PubMed, EMBASE, Web of Science, and Cochrane Library databases. Outcomes of interest included visual outcomes, anatomic variables, and adverse events.Six studies enrolling a total of 346 patients were included. The weighted mean differences (WMDs) of the mean changes in LogMAR VA when comparing PDT with anti-VEGF were -0.02 (95 % confidence interval [CI]: -0.12-0.08) at 3 months, 0.02 (95 % CI: -0.12-0.16) at 6 months, 0.02 (95 % CI: -0.15-0.18) at 12 months, and -0.17 (95 % CI: -0.90-0.55) at 24 months. There were no significant differences between the two groups at any of the time points. PDT was found to be associated with greater reduction of central retinal thickness (CRT) at six months (WMD: 44.94; 95 % CI: 16.44-73.44; P?=?0.002), and it was superior to anti-VEGF therapy in achieving complete polyp regression (odd ratio, OR: 6.85; 95 % CI: 2.15-21.79; P?=?0.001).Rates of adverse events did not differ significantly between the two treatments.PDT appeared to result in greater CRT reduction at six months and higher polyp regression rate. However, the two treatments appear to be comparable in terms of best corrected visual acuity change and adverse events.
| S-EPMC4513969 | biostudies-literature
Project description:Three new amide alkaloids piperlongumamides A-C (1–3), together with 12 known ones (4–15), were isolated from the fruits of Piper longum. The structures of the new isolates were determined using spectroscopic data analyses. Cytotoxic activity of these amides against HL-60 (human leukemia), A-549 (human lung cancer), MCF-7 (human breast cancer), SMMC-7721 (human liver cancer) and SW480 (human rectal cancer) cell lines were evaluated. Piperchabamide B (11) exhibited weak inhibitory activity against HL-60 (IC50 = 21.32 μM ), A-549 (IC50 = 23.82 μM ) and MCF-7 (IC50 = 16.58 μM ) cell lines. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s13659-013-0073-0 and is accessible for authorized users.
| S-EPMC4131601 | biostudies-literature
Project description: Not available
| S-EPMC7202375 | biostudies-literature
Project description:BACKGROUND:Neovascular glaucoma (NVG) is a potentially blinding secondary glaucoma. It is caused by the formation of abnormal new blood vessels which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) agents are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGFs for the control of intraocular pressure (IOP) in NVG. OBJECTIVES:To compare the IOP lowering effects of intraocular anti-VEGF agents to no anti-VEGF treatment, as an adjunct to existing modalities for the treatment of NVG. SEARCH METHODS:We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 January 2013. SELECTION CRITERIA:We included randomized controlled trials (RCTs) and quasi-RCTs of people treated with anti-VEGF agents for NVG. DATA COLLECTION AND ANALYSIS:Two authors independently assessed the search results for trials to be included in the review. Discrepancies were resolved by discussion with a third author. Since no trial met our inclusion criteria, no assessment of risk of bias or meta-analysis was undertaken. MAIN RESULTS:No RCTs were found that met the inclusion criteria for this review. Two RCTs of anti-VEGF agents for treating NVG were not included in the review due to the heterogeneity and uncontrolled assignment of adjunct treatments received by the study participants. AUTHORS' CONCLUSIONS:Currently available evidence is insufficient to evaluate the effectiveness of anti-VEGF treatments, such as intravitreal ranibizumab or bevacizumab, as an adjunct to conventional treatment in lowering IOP in NVG. Well designed RCTs are needed to address this issue, particularly trials that evaluate long-term (at least six months) benefits and risks since the effects of anti-VEGF agents may be short-term only. An RCT comparing anti-VEGF agents with no anti-VEGF agents taking into account the need for co-interventions, such as panretinal photocoagulation (PRP), glaucoma shunt procedures, cyclodestructive procedures, cataract surgery, and deep vitrectomy, could be of use to investigate the additional beneficial effect of anti-VEGF agents in treating NVG. Since decisions for when and which co-interventions should be used are based on clinical criteria, they would not be appropriate for randomization. However, the design of a study on this topic should aim to balance groups by stratification of co-intervention at time of randomization or by enrolling a sufficient number of participants to conduct subgroup analysis by co-interventions (ideally 15 participants per treatment group for each subgroup). Alternatively, the inclusion criteria for a trial could limit participants to those who receive the same co-intervention.
| S-EPMC4261636 | biostudies-literature