MOLECULAR DOCKING ANALYSIS OF THIRTEEN COMPOUNDS AS MODULATOR OF IONOTROPIC GLUTAMATE RECEPTOR

Objectives: Ionotropic glutamate receptors (iGluRs) play a key role in the development and function of the nervous system. They also play an important in memory and learning process. They are implicated in various pathological conditions such as Alzheimer's, Epilepsy, Huntington's, and Parkinson's diseases. This prompted us to carry out the present study on 13 selected compounds.Methods: These 13 compounds were evaluated on the docking behavior of iGluR-2 (iGluR2) using PatchDock. In addition, molecular physicochemical, drug-likeness, absorption, distribution, metabolism, and excretion analyses were also carried out.Results: The molecular physiochemical analysis revealed that all the 13 ligands showed nil violation and complied well with the Lipinski's rule of five. ADME analysis showed that all the ligands (except ligands 1 and 12) predicated to have high gastrointestinal absorption property. Docking studies revealed that ligand 8 (dopamine) showed the highest atomic contact energy (ACE) (−78.14 kcal/mol), while ligand 9 (6-hydroxydopamine) showed the least ACE (−14.34 kcal/mol) with that of iGluR2. Similarly, ligand 8 (dopamine) has shown to interact with Ser 142 amino acid residue of iGluR2.Conclusion: Thus, the present study showed the potential of 13 compounds as a modulator of iGluR-2

PHYTIC ACID (MYO-INOSITOL HEXAPHOSPHATE)- A PROMISING PHARMACEUTICAL AGENT: A REVIEW

Phytic acid (myo-inositol hexaphosphate) has gained much attention among researchers for its therapeutic value. This review focuses on pharmacological activities of phytic acid, which have been demonstrated by pre-clinical studies. Anti-carcinogenic, antioxidant, antidiabetic, hypolipidemic, anti-angiogenic, and immunomodulation are the most extensively studied pharmacological activities of phytic acid. In addition to these, phytic acid and its derivatives also possess enzyme inhibitory activities against few key enzymes such as 5-alpha reductase, aldose reductase, cyclooxygenase, lipase, matrix metalloproteinase-2 & 9, pepsin, polyphenol oxidase, protease, β-secretase, tyrosinase, and xanthine oxidase were emphasized. The profound pharmacological activities of phytic acid have proven to be a good therapeutic agent and could be employed in preventing as well as treating such diseases

Role of herbal medicines in vitiligo treatment - current status and future perspectives

Vitiligo is a depigmentation disorder with complex causes. Nonetheless, recent progress has been made to unravel the pathophysiology of vitiligo. In this review, we provide an overview of the currently known herbal medicine for vitiligo treatment and also highlighted the herbs that have been used in clinical trials. In view of traditional uses, herbs such as Ammi visnaga L., Angelica sinensis, Eclipta alba L, Ginkgo biloba, Picrorhiza kurroa Royle Ex Benth, and Psoralea corylifolia L, have been highlighted. Enormous efforts in vitiligo drug discovery are currently needed. Interleukin-17 inhibition, tumor necrosis factor-alpha inhibition, heat shock protein-70i (HSP70i) inhibition, keratinocyte turnover modulators, and regulatory T cells (Tregs) modulators have been discussed as promising new targets for vitiligo drug development. Thus, we strongly believe that this review may be useful for rationalize new herbal drug for vitiligo treatment

PREDICTING THE BIODEGRADABILITY NATURE OF IMIDAZOLE AND ITS DERIVATIVES BY MODULATING TWO HISTIDINE DEGRADATION ENZYMES (UROCANASE AND FORMIMINOGLUTAMASE) ACTIVITIES

Objectives: The biodegradation pathway of substituted imidazole ring compounds has been reported to have close analogy to the histidine degradation pathway. This prompted the present study to be carried out on 12 selected imidazole and its derivatives which are 1-imidazole, 1, 2-dimethylimidazole, 1-ethyl imidazole, 2-ethyl-4-methylimidazole, 2-isopropylimidazole, 2-Isopropyl-4-nitro-1H-imidazole, 1-methylimidazole, 2-methyl-5-nitroimidazole, 2-methyl-1-vinylimidazole, 1-nitro imidazole, 1-phenyl imidazole, and 1-vinylimidazole.Methods: The imidazole and its derivatives were evaluated on the docking behavior of urocanase and formiminoglutamase using PatchDock. In addition, molecular physicochemical, drug-likeness, absorption, distribution, metabolism, and excretion analyses (ADME) were done.Results: The molecular physicochemical analysis revealed that all the tested ligands showed nil violation and complied well with the Lipinski's rule of five. ADME analysis showed that 1-phenylimidazole alone predicated to have cytochrome P450 1A2 inhibition effect. Docking studies revealed that 1-nitroimidazole showed the least atomic contact energy with both targeted enzymes (urocanase and FIGase).Conclusion: Inhibition of both enzymes (urocanase and FIGase) might show poor biodegradability nature. Thus, we can predict biodegradability nature of imidazloe and its derivatives by modulating two histidine degradation enzymes activities

Molecular docking analysis of Carica papaya Linn constituents as antiviral agent

Carica papaya (papaya) fruits are available throughout the world and it is well accepted as food or as a quasi-drug. Aqueous papaya leaves extract have been used as treatment for dengue fever. This prompted us to carry out the docking study on these nine selected ligands (phyto-constituents of papaya) which are carpaine, dehydrocarpaine I and II, cardenolide, p-coumaric acid, chlorogenic acid, caricaxanthin, violaxanthin and zeaxanthin. These phyto-constituents were evaluated on the docking behaviour of dengue serotype 3 RNA-dependent RNA polymerase (RdRp); influenza A (H1N9) virus neuraminidase (NA); chikungunya virus glycoprotein (E3-E2-E1) and chikungunya virus non-structural protein2 (nsP2) protease using Discovery Studio Version 3.1. In addition, molecular physicochemical, drug-likeness, ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) and TOPKAT (Toxicity Prediction by Komputer Assisted Technology) analyses were done. The molecular physicochemical analysis revealed that cardenolide and p-coumaric acid (2 ligands) complied with Lipinski’s rule of five. Dehydrocarpaine II, cardenolide, caricaxanthin, violaxanthin and zeaxanthin all the five ligands were predicted to have plasma protein binding (PPB) effect. Docking studies and binding free energy calculations revealed that p-coumaric acid exhibited very least binding energy irrespective of its target protein. Hence, the results of this present study exhibited the potential of these nine ligands as antiviral agent

Endophytic fungi and bioactive metabolites production: an update

Endophytic fungi are unique microbes that reside in the plant tissues and cause no harm or any symptoms of diseases. Although plants are the major source of modern drugs, there is a continuous search for new sources to obtain new lead molecules, with higher biological properties, for treating various diseases. Many plants are associated with several kinds of endophytic fungi capable of producing bioactive secondary metabolites. Thus, endophytic fungi can act as a reservoir of bioactive principles which are yet to be explored in detail. In addition, plant-endophytic fungal association stimulates plant growth, increase resistance towards phyto-pathogens, suppress the weed, and increase tolerance to abiotic and biotic stresses. In this chapter, various aspects of endophytic fungi including their symbiosis with plants, biological implications and important secondary metabolites production are discussed in detail. This information would certainly help to improve the pace of modern drug discovery

In silico analysis of Mentha pipertia (phyto-constituents) as HMG coa reductase and squalene synthase inhibitors

Mentha piperita has been well known for its hypolipidemic activity. This prompted the present study to be carried out on a selected 12 phyto-constituents of Mentha piperita which are naringin, eriodictyol, eriodictyol 7-glucuronide, eriocitrin, hesperidin, isorohifolin, luteolin 7-glucoside, diosmin, rosmarinic acid, piperitoside, menthoside and caffeic acid. These phyto-constituents were evaluated on the docking behaviour of HMG CoA reductase (HMGR) and Squalene synthase (SQS) using Discovery Studio Version 3.1. In addition, molecular physicochemical, drug-likeness, ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) and TOPKAT (Toxicity Prediction by Komputer Assisted Technology) analyses were done. The molecular physicochemical analysis revealed that eriodictyol, rosmarinic acid and caffeic acid (3 ligands) complied with Lipinski’s rule of five. ADMET analysis showed that eriodictyol and caffeic acid exhibited good intestinal absorption property. Docking studies and binding free energy calculations revealed that menthoside (-70.0 kcal/mol) and piperitoside (-65.32 kcal/mol) exhibited the maximum interaction energy with HMGR and SQS respectively. Caffeic acid exhibited very least binding energy irrespective of its target protein. Caffeic acid showed interaction with Leu546 and Gln212 amino acid residue of HMGR and SQS. Hence, the results of this present study exhibited the potential of these twelve ligands as hypolipidemic agents

Single mode tapered fiber-optic interferometer based refractive index sensor and its application to protein sensing

We demonstrate refractive index sensors based on single mode tapered fiber and its application as a biosensor. We utilize this tapered fiber optic biosensor, operating at 1550 nm, for the detection of protein (gelatin) concentration in water. The sensor is based on the spectroscopy of mode coupling based on core modes-fiber cladding modes excited by the fundamental core mode of an optical fiber when it transitions into tapered regions from untapered regions. The changes are determined from the wavelength shift of the transmission spectrum. The proposed fiber sensor has sensitivity of refractive index around 1500 nm/RIU and for protein concentration detection, its highest sensitivity is 2.42141 nm/%W/V

Non-contact tests for identifying people at risk of primary angle closure glaucoma

BACKGROUND: Primary angle closure glaucoma (PACG) accounts for 50% of glaucoma blindness worldwide. More than three-quarters of individuals with PACG reside in Asia. In these populations, PACG often develops insidiously leading to chronically raised intraocular pressure and optic nerve damage, which is often asymptomatic. Non-contact tests to identify people at risk of angle closure are relatively quick and can be carried out by appropriately trained healthcare professionals or technicians as a triage test. If the test is positive, the person will be referred for further specialist assessment. OBJECTIVES: To determine the diagnostic accuracy of non-contact tests (limbal anterior chamber depth (LACD) (van Herick test); oblique flashlight test; scanning peripheral anterior chamber depth analyser (SPAC), Scheimpflug photography; anterior segment optical coherence tomography (AS-OCT), for identifying people with an occludable angle. SEARCH METHODS: We searched the following bibliographic databases 3 October 2019: CENTRAL; MEDLINE; Embase; BIOSIS; OpenGrey; ARIF and clinical trials registries. The searches were limited to remove case reports. There were no date or language restrictions in the searches. SELECTION CRITERIA: We included prospective and retrospective cross-sectional, cohort and case-control studies conducted in any setting that evaluated the accuracy of one or more index tests for identifying people with an occludable angle compared to a gonioscopic reference standard. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and quality assessment using QUADAS2 for each study. For each test, 2 x 2 tables were constructed and sensitivity and specificity were calculated. When four or more studies provided data at fixed thresholds for each test, we fitted a bivariate model using the METADAS macro in SAS to calculate pooled point estimates for sensitivity and specificity. For comparisons between index tests and subgroups, we performed a likelihood ratio test comparing the model with and without the covariate. MAIN RESULTS: We included 47 studies involving 26,151 participants and analysing data from 23,440. Most studies were conducted in Asia (36, 76.6%). Twenty-seven studies assessed AS-OCT (analysing 15,580 participants), 17 studies LACD (7385 participants), nine studies Scheimpflug photography (1616 participants), six studies SPAC (5239 participants) and five studies evaluated the oblique flashlight test (998 participants). Regarding study quality, 36 of the included studies (76.6%) were judged to have a high risk of bias in at least one domain.The use of a case-control design (13 studies) or inappropriate exclusions (6 studies) raised patient selection concerns in 40.4% of studies and concerns in the index test domain in 59.6% of studies were due to lack of masking or post-hoc determination of optimal thresholds. Among studies that did not use a case-control design, 16 studies (20,599 participants) were conducted in a primary care/community setting and 18 studies (2590 participants) in secondary care settings, of which 15 investigated LACD. Summary estimates were calculated for commonly reported parameters and thresholds for each test; LACD ≤ 25% (16 studies, 7540 eyes): sensitivity 0.83 (95% confidence interval (CI) 0.74, 0.90), specificity 0.88 (95% CI 0.84, 0.92) (moderate-certainty); flashlight (grade1) (5 studies, 1188 eyes): sensitivity 0.51 (95% CI 0.25, 0.76), specificity 0.92 (95% CI 0.70, 0.98) (low-certainty); SPAC (≤ 5 and/or S or P) (4 studies, 4677 eyes): sensitivity 0.83 (95% CI 0.70, 0.91), specificity 0.78 (95% CI 0.70, 0.83) (moderate-certainty); Scheimpflug photography (central ACD) (9 studies, 1698 eyes): sensitivity 0.92 (95% CI 0.84, 0.96), specificity 0.86 (95% CI 0.76, 0.93) (moderate-certainty); AS-OCT (subjective opinion of occludability) (13 studies, 9242 eyes): sensitivity 0.85 (95% CI 0.76, 0.91); specificity 0.71 (95% CI 0.62, 0.78) (moderate-certainty). For comparisons of sensitivity and specificity between index tests we used LACD (≤ 25%) as the reference category. The flashlight test (grade 1 threshold) showed a statistically significant lower sensitivity than LACD (≤ 25%), whereas AS-OCT (subjective judgement) had a statistically significant lower specificity. There were no statistically significant differences for the other index test comparisons. A subgroup analysis was conducted for LACD (≤ 25%), comparing community (7 studies, 14.4% prevalence) vs secondary care (7 studies, 42% prevalence) settings. We found no evidence of a statistically significant difference in test performance according to setting. Performing LACD on 1000 people at risk of angle closure with a prevalence of occludable angles of 10%, LACD would miss about 17 cases out of the 100 with occludable angles and incorrectly classify 108 out of 900 without angle closure. AUTHORS' CONCLUSIONS: The finding that LACD performed as well as index tests that use sophisticated imaging technologies, confirms the potential for this test for case-detection of occludable angles in high-risk populations. However, methodological issues across studies may have led to our estimates of test accuracy being higher than would be expected in standard clinical practice. There is still a need for high-quality studies to evaluate the performance of non-invasive tests for angle assessment in both community-based and secondary care settings