University of Calcutta (informally known as Calcutta University or CU) is a collegiate public state university located in Kolkata, West Bengal, India.&nbsp;Within India it is recognized as a &quot;Five-Star University&quot; and accredited &quot;A&quot; Grade by National Assessment and Accreditation Council.

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The University of Calcutta has secured the Fifth position among the Universities of India in the prestigious &quot;Indian University Ranking 2019&quot; list, released by the NIRF of the Ministry of Human Resource Development, Government of India.

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It was established on 24 January 1857, and was one of the first institutions in Asia to be established as a multidisciplinary and Western-style university. Its alumni and faculty include several heads of state, heads of government, social reformers, prominent artists, only academy award winner and Dirac medal winner in India, many Fellows of the Royal Society and five Nobel laureates as of 2019 which is highest in South Asia.

University Of Calcutta

Chemical Technology

Cadmium (Cd) imparts nephrotoxicity via triggering oxidative stress and pathological signal transductions in renal cells. The present study was performed to explore the protective mechanism of carnosic acid (CA), a naturally occurring antioxidant compound, against cadmium chloride (CdCl2)-provoked nephrotoxicity employing suitable in vitro and in vivo assays. CA (5 μM) exhibited an anti-apoptotic effect against CdCl2 (40 μM) in normal kidney epithelial (NKE) cells evidenced from cell viability, image, and flow cytometry assays. In this study, CdCl2 treatment enhanced oxidative stress by triggering free radical production, suppressing the endogenous redox defence system, and inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) activation inNKE cells andmouse kidneys. Moreover, CdCl2 treatment significantly endorsed apoptosis and fibrosis via activation of apoptotic and transforming growth factor (TGF)-β1/mothers against decapentaplegic homolog (Smad)/collagen IV signalling pathways, respectively. In contrast, CA treatment significantly attenuated Cd-provoked nephrotoxicity via inhibiting free radicals, endorsing redox defence, suppressing apoptosis, and inhibiting fibrosis in renal cells in both in vitro and in vivo systems. In addition, CA treatment significantly (p &lt; 0.05-0.01) restored blood and urine parameters to near-normal levels in mice. Histological findings further confirmed the protective role of CA against Cd-mediated nephrotoxicity. Molecular docking predicted possible interactions between CA and Nrf2/TGF-β1/Smad/collagen IV. Hence, CA was found to be a potential therapeutic agent to treat Cd-mediated nephrotoxicity. © 2019 by the authors.

World University root node

Fulltext

Molecules

Carnosic acid attenuates cadmium induced nephrotoxicity by inhibiting oxidative stress, promoting Nrf2/HO-1 signalling and impairing TGF-β1/Smad/collagen IV signalling

The N-methyl-D-aspartate (NMDA) is the family of glutamate receptor, which is involved in controlling synaptic plasticity and memory function; but overactivation of this receptor results to excess intracellular calcium formation, triggers neuronal injury and also involves in several pathologies. Both ligand- and structure-based quantitative structure-activity relationship (QSAR), pharmacophore, docking and simulation studies have been performed on a set of structurally diverse inhibitors to explore prime molecular structural features involve for specific binding to NMDA, and vis-à-vis inhibiting enzyme activity. 3D QSAR studies, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models showed the importance of steric, electrostatic and hydrophobic features; while hydrogen bond acceptor and hydrophobic features are depicted as important pharmacophore features of the molecule. Molecular docking and simulation studies corroborated the consequence of the features obtained from ligand-based Bayesian model (AUROCcv = 0.878); 3D QSAR CoMFA (R2 = 0.895, se = 0.513, Q2 = 0.602, R2pred = 0.673); CoMSIA (R2 = 0.877, se = 0.555, Q2 = 0.615, R2pred = 0.727); hologram QSAR (Q2 = 0.812, R2 = 0.941, R2pred = 0.772), and pharmacophore models (Q2 = 0.926, R2 = 0.927, R2pred = 0.621). Presence of aromatic ring, hetero and halogen atoms along with alkyl group of molecular scaffold shows their importance for binding affinity to NMDA receptor. Stability of the complex is adjudged by both docking and simulation studies. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

GENERAL

Structural Chemistry

Exploration of structural and physicochemical properties of small molecules to inhibit NMDA functionality

Background: Wound is an inherent process to regenerate the cellular cohesion of tissue. Present study deal with the accelerating potentiality of rhamnolipid produced by P. aeruginosa C2 using fat of Catla catla fish as an economic substrate to heal wound in a shorter time. Methodology: An ointment containing rhamnolipid (5 g/l) was administered on the back of each wister rat after creating excision wound of 50 mm2. The examined parameters were percentage wound reduction, tissue tensile strength, DNA, protein, hexosamine content and histological study of regenerated tissue and TNF α estimation from blood serum. Main findings: Rhamnolipid enhanced the rate of wound contraction within 10 days in comparison to untreated control group (p &lt; 0.05). The higher tensile strength of the rhamnolipid treated group signified (p &lt; 0.05) improved collagenesis which was supported by remarkably higher DNA, total protein and hexosamine content of the regenerated tissue at the wound site in comparison to untreated control group. Diminishing level of TNF-α in serum, histopathological studies revealed significant healing effect of rhamnolipid. Moreover activity of rhamnolipid against Staphylococcus aureus ATCC6588 may have contributed towards wound healing by protecting the wound site from bacterial contamination. Conclusions: The results of this study have expressed that rhamnolipid can be used as a wound healing material for excision wound. Rhamnolipid can provide additional advantage in healing by showing protection from bacterial infection. © 2018

Wound Medicine

Excision wound healing activity of a common biosurfactant produced by Pseudomonas sp.

Bacterial extracellular polymeric substances, which are basically bacterial metabolites, have currently become a subject of great concern of modern day microbiologists and biotechnologists. Among these metabolites, bacterial exopolysaccharides or EPS, in particular, have gained a significant importance. EPS are formed by the bacteria in their late exponential or stationary phase of growth under special situations for specific purposes. They take part in the formation of bacterial biofilms. There is a great diversity in the types of EPS. Strikingly enough, a same species of bacterium can produce different types of EPS under different situations. The importance of EPS is largely because of their different applications in various industries. Now that the bacterial EPS has got the potentiality to become an upcoming tool in various futuristic applications of human benefit, the focus currently develops towards how better they can be produced in the laboratory by promoting the favorable factors for their production. While studying with different EPS forming bacteria, both the intrinsic factors like genetic configuration of the bacteria and the extrinsic factors like culture conditions under the influence of different physico-chemical parameters in order to maximize the EPS production have been taken into consideration. Both the factors have proved their worth. Hence, towards a better outcome for EPS production, it is indicated that a genetic manipulation of the bacteria should be synchronized with a proper selection of its culture condition by controlling different physico-chemical parameters. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Applied Microbiology and Biotechnology

Towards a better production of bacterial exopolysaccharides by controlling genetic as well as physico-chemical parameters

Engaging Raman spectroscopy as a primary tool, we investigated the early events of insulin fibrilization and determined the structural content present in oligomer and protofibrils that are formed as intermediates in the fibril formation pathway. Insulin oligomer, as obtained upon incubation of zinc-free insulin at 60 °C, was mostly spherical in shape, with a diameter of 3-5 nm. Longer incubation produced "necklace"-like beaded protofibrillar assembly species. These intermediates eventually transformed into 5-8 nm thick fibers with smooth surface texture. A broad amide I band in the Raman spectrum of insulin monomer appeared at 1659 cm -1 , with a shoulder band at 1676 cm -1 . This signature suggested the presence of major helical and extended secondary structure of the protein backbone. In the oligomeric state, the protein maintained its helical imprint (∼50%) and no substantial increment of the compact cross-β-sheet structure was observed. A nonamide helix signature band at 940 cm -1 was present in the oligomeric state, and it was weakened in the fibrillar structure. The 1-anilino-8-naphthalene-sulfonate binding study strongly suggested that a collapse in the tertiary structure, not the major secondary structural realignment, was the dominant factor in the formation of oligomers. In the fibrillar state, the contents of helical and disordered secondary structures decreased significantly and the β-sheet amount increased to ∼62%. The narrow amide I Raman band at 1674 cm -1 in the fibrillar state connoted the formation of vibrationally restricted highly organized β-sheet structure with quaternary realignment into steric-zipped species. © 2018 American Chemical Society.

ACS Omega

Structural Insight of Amyloidogenic Intermediates of Human Insulin

Matrix metalloproteinase-2 (MMP-2) is a potential target in anticancer drug discovery due to its association with angiogenesis, metastasis and tumour progression. In this study, 67 glutamic acid derivatives, synthesized and evaluated as MMP-2 inhibitors, were taken into account for multi-QSAR modelling study (regression-based 2D-QSAR, classification-based LDA-QSAR, Bayesian classification QSAR, HQSAR, 3D-QSAR CoMFA and CoMSIA as well as Open3DQSAR). All these QSAR studies were statistically validated individually. Regarding the 3D-QSAR analysis, the Open3DQSAR results were better than CoMFA and CoMSIA, although all these 3D-QSAR models supported each other. The importance of biphenylsulphonyl moiety over phenylacetyl/naphthylacetyl moieties was established due to its association with favourable steric and hydrophobic characters. HQSAR, LDA-QSAR and Bayesian classification QSAR studies also suggested that the biphenylsulphonamido group was better than the phenylacetylcarboxamido function. Additionally, glutamines were proven to be far better inhibitors than isoglutamines. Observations obtained from the current study were revalidated and supported by the earlier reported molecular modelling studies. Depending on these observations, newer glutamic acid-based compounds may be designed further in future for potent MMP-2 inhibitory activity. © 2017 Informa UK Limited, trading as Taylor & Francis Group.

SAR and QSAR in Environmental Research

Multiple molecular modelling studies on some derivatives and analogues of glutamic acid as matrix metalloproteinase-2 inhibitors$

We have evaluated the LDH inhibitory property of novel pyrazolo[4′,3′:5,6][1,4]oxathiino[2,3-b]pyrazine derivatives which have been synthesized from easily available starting materials through a one-pot protocol that offers the use of elemental sulfur as the sulfur source. These newly synthesized compounds may aid to drug development for neoplastic and non-neoplastic diseases characterized by increased glucose metabolism. Additionally, they may act as suitable starting materials which can be further structurally modified for the development of new LDH inhibitors with higher efficacy and specificity. © Georg Thieme Verlag KG Stuttgart. New York.

Chemistry

Drug Research

Synthesis of Novel tricyclic pyrazolo(1,4)oxathiinopyrazines and Evaluation of Their Competency Towards the Inhibition of Lactate Dehydrogenase Activity-Inhibition of LDH Activity

Capsaicin is the principal constituent of oleoresin capsicum, or pepper spray, as it is commonly known. Pepper sprays are frequently used in riot control situations by defence organizations all over the world to deal with uncontrolled civil or criminal disturbances. Although capsaicin is noted for its irritant and inflammatory properties, the ocular profile of capsaicin has not been specifically studied and interpreted. The present review analyses the mammalian opthalmological profile of capsaicin and its pharmacological and toxicological manifestations including capsaicin induced corneal changes, neurogenic inflammation, neuroprotective influences on retinal ganglion cells (RGCs), depletion of neuropeptide content in sensory nerve terminals etc. Substantial views on the capsaicin receptor Transient Receptor Potential Vanilloid V1 (TRPV1), its presence, significance and capsaicin induced mediations have been presented. Studies conducted previously on the reversal of capsaicin evoked ocular responses have been briefly demonstrated. In this regard, TRPV1 antagonists (especially the competitive antagonist Capsazepine) have been indicated as potential candidates in mitigating or alleviating capsaicin elicited ocular responses. The review overall is a comprehensive perspective of the ocular inflammatory and pharmacological responses generated on exposure to capsaicin and concludes suggesting a possible regulatory framework for relief from the same presumably by the employment of specialized and target specific TRPV1 antagonists. © 2017 Elsevier B.V.

European Journal of Pharmacology

Capsaicin, the primary constituent of pepper sprays and its pharmacological effects on mammalian ocular tissues

The present studies have been executed to explore the protective mechanism of carnosic acid (CA) against NaAsO 2 -induced hepatic injury. CA exhibited a concentration dependent (1-4 μM) increase in cell viability against NaAsO 2 (12 μM) in murine hepatocytes. NaAsO 2 treatment significantly enhanced the ROS-mediated oxidative stress in the hepatic cells both in in vitro and in vivo systems. Significant activation of MAPK, NF-κB, p53, and intrinsic and extrinsic apoptotic signaling was observed in NaAsO 2 -exposed hepatic cells. CA could significantly counteract with redox stress and ROS-mediated signaling and thereby attenuated NaAsO 2 -mediated hepatotoxicity. NaAsO 2 (10 mg/kg) treatment caused significant increment in the As bioaccumulation, cytosolic ATP level, DNA fragmentation, and oxidation in the liver of experimental mice (n = 6). The serum biochemical and haematological parameters were significantly altered in the NaAsO 2 -exposed mice (n = 6). Simultaneous treatment with CA (10 and 20 mg/kg) could significantly reinstate the NaAsO 2 -mediated toxicological effects in the liver. Molecular docking and dynamics predicted the possible interaction patterns and the stability of interactions between CA and signal proteins. ADME prediction anticipated the drug-likeness characteristics of CA. Hence, there would be an option to employ CA as a new therapeutic agent against As-mediated toxic manifestations in future. © 2018 Sonjit Das et al.

Oxidative Medicine and Cellular Longevity

Carnosic acid, a natural diterpene, attenuates arsenic-induced hepatotoxicity via reducing oxidative stress, MAPK activation, and apoptotic cell death pathway

Background: Metabolic syndrome is a matrix of different metabolic disorders which are the leading cause of death in human beings. Peroxysome proliferated activated receptor (PPAR) is a nuclear receptor involved in metabolism of fats and glucose. Objective: In order to explore structural requirements for selective PPAR modulators to control lipid and carbohydrate metabolism, the multi-cheminformatics studies have been performed. Methods: In silico modeling studies have been performed on a diverse set of PPAR modulators through quantitative structure-activity relationship (QSAR), pharmacophore mapping and docking studies. Results: It is observed that the presence of an amide fragment (-CONHRPh) has a detrimental effect while an aliphatic ether linkage has a beneficial effect on PPARα modulation. On the other hand, the presence of an amide fragment has a positive effect on PPARδ modulation, but the aliphatic ether linkage and substituted aromatic ring in the molecular scaffold are very much essential for imparting potent and selective PPARγ modulation. Negative ionizable features (i.e. polar fragments) must be present in PPARδ and α modulators, but a hydrophobic feature is the prime requirement for PPARγ modulation. Conclusion: Here, the essential structural features have been explored for selective modulation of each subtype of PPAR in order to design new modulators with improved activity/selectivity. © 2018 Bentham Science Publishers.