Synthesis and biological evaluation of aeruginosin based compounds and self-assembly of glucosamine based compounds

Aeruginosins are a family of marine natural products containing mostly non-proteogenic amino acids. These compounds contain a common 2-carboxy-6-hydroxy-octaindole (Choi) rigid bicyclic structure. Many aeruginosins are inhibitors for enzymes involved in the blood coagulation cascade, such as thrombin and Factor VIIa. In order to understand the structure activity relationship (SAR) of the aeruginosins and to discover novel anticoagulants with potentially improved inhibitory and pharmacokinetic properties, in the first part of my thesis I have discussed, synthesis of a series of novel analogs of aeruginosin 298-A, in which the Choi will be replaced with L-proline and oxygenated Choi analogs, and the Argol is replaced with various other functionalities. The preparation of oxygenated Choi analogs starting from glucose using a new method has been discussed. In the second part of my dissertation, I have discussed the design, synthesis and self–assembly of glucosamine based hydro and organogelators. Carbohydrate-based low molecular weight gelators are an interesting class of molecules with many potential applications. A series of amides and ureas were prepared from the protected D-glucosamine from the corresponding acid chloride and isocyanates. The self-assembling properties of these compounds were studied in several solvents, including water and aqueous solutions. Most of these compounds were found to be efficient low molecular weight hydrogelators (LMHGs) for aqueous solutions. The preparation and characterization of these compounds will be elaborated

An evaluation of congenital talipes equinovarus patients treated by various methods

Background: Idiopathic congenital talipes equinovarus is one of the commonest congenital anomaly. Although treatment provides many options, near universal agreement exists that initial management should consist of gentle manipulation of the affected foot. In developing country like India presentation is extremely variable from soon after birth to very late childhood and irregular follow up makes treatment more difficult.Methods: 100 cases of congenital talipes equinovarus who attended the Orthopedics OPD of our hospital (March 2013  to 2016) were taken up. In neonates with delicate skin, the passive manipulation was demonstrated to the mother which they did 5-6 times daily. The application of plaster of Paris cast and passive manipulation was done every 15th day upto 3 months of age. After the 3-month age, passive manipulation was done every 3 weeks. If no normalization, surgery was advised and done to correct the resistant component accordingly. All the analyses were performed in R-programming language (R- 3.0.0).Results: 6 cases,10 feet were lost during follow-up. Results were assessed in 134 feet, 128 cases managed conservatively, 13 surgically. Results were assessed according to clinical, radiological criteria of Beatson and Pearson. 13 feet were operated of 144 feet,11 cases posteromedial soft tissue release (PMSTR) was done. In two Joshi’s external stabilizing system (JESS) fixator was applied.Conclusions: Majority of cases can be treated successfully by conservative means and only in 11 cases PMSTR was done, 2 cases of relapsed feet JESS was applied

Characterization of the Lactobacillus isolated from different curd samples

Lactic acid bacteria are commonly found in the fermented dairy products. Lactobacillus is a genus of lactic acid bacteria and described as heterogeneous group of regular, non-spore forming, gram-positive, rod shaped, non-motile bacteria and absence of catalase enzyme. The aim of this study was to isolate Lactobacillus from different curd samples. A total of 14 curd samples were collected from the local areas of Gurgaon (Haryana) and Lakshmangarh (Rajasthan). From these, 28 isolates were obtained by growing on de Man, Rogosa and Sharpe (MRS) agar medium and characterised by their phenotypic characteristics. The Lactobacillus isolates also possess homofermentative and heterofermentative characteristics.Key words: Lactobacillus, curd, microorganis

Review of Ligand Specificity Factors for CYP1A Subfamily Enzymes from Molecular Modeling Studies Reported to-Date

The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the advent of several types of cancer. The development of selective inhibitors for these P450 enzymes, mitigating procarcinogenic oxidative effects, has been the focus of many studies in recent years. CYP1A1 is mainly found in extrahepatic tissues while CYP1A2 is the major CYP enzyme in human liver. Many molecules have been found to be metabolized by both of these enzymes, with varying rates and/or positions of oxidation. A complete understanding of the factors that govern the specificity and potency for the two CYP 1A enzymes is critical to the development of effective inhibitors. Computational molecular modeling tools have been used by several research groups to decipher the specificity and potency factors of the CYP1A1 and CYP1A2 substrates. In this review, we perform a thorough analysis of the computational studies that are ligand-based and protein-ligand complex-based to catalog the various factors that govern the specificity/potency toward these two enzymes

Review of Ligand Specificity Factors for CYP1A Subfamily Enzymes from Molecular Modeling Studies Reported to-Date

The cytochrome P450 (CYP) family 1A enzymes, CYP1A1 and CYP1A2, are two of the most important enzymes implicated in the metabolism of endogenous and exogenous compounds through oxidation. These enzymes are also known to metabolize environmental procarcinogens into carcinogenic species, leading to the advent of several types of cancer. The development of selective inhibitors for these P450 enzymes, mitigating procarcinogenic oxidative effects, has been the focus of many studies in recent years. CYP1A1 is mainly found in extrahepatic tissues while CYP1A2 is the major CYP enzyme in human liver. Many molecules have been found to be metabolized by both of these enzymes, with varying rates and/or positions of oxidation. A complete understanding of the factors that govern the specificity and potency for the two CYP 1A enzymes is critical to the development of effective inhibitors. Computational molecular modeling tools have been used by several research groups to decipher the specificity and potency factors of the CYP1A1 and CYP1A2 substrates. In this review, we perform a thorough analysis of the computational studies that are ligand-based and protein-ligand complex-based to catalog the various factors that govern the specificity/potency toward these two enzymes

Synthesis and Characterization of pH Responsive D-Glucosamine Based Molecular Gelators

Small molecular gelators are a class of compounds with potential applications for soft biomaterials. Low molecular weight hydrogelators are especially useful for exploring biomedical applications. Previously, we found that 4,6-O-benzylidene acetal protected D-glucose and D-glucosamine are well-suited as building blocks for the construction of low molecular weight gelators. To better understand the scope of D-glucosamine derivatives as gelators, we synthesized and screened a novel class of N-acetylglucosamine derivatives with a p-methoxybenzylidene acetal protective group. This modification did not exert a negative influence on the gelation. On the contrary, it actually enhanced the gelation tendency for many derivatives. The introduction of the additional methoxy group on the phenyl ring led to low molecular weight gelators with a higher pH responsiveness. The resulting gels were stable at neutral pH values but degraded in an acidic environment. The release profiles of naproxen from the pH responsive gels were also analyzed under acidic and neutral conditions. Our findings are useful for the design of novel triggered release self-assembling systems and can provide an insight into the influence of the the structure on gelation

ANTIMICROBIAL ACTIVITY AND PHYTOCHEMICAL SCREENING OF LEAVES EXTRACT OF MORINDA PUBESCENS LINN. PLANT

The ethanolic extracts of leaves of Morinda pubescens Linn. were explored for their phytochemical constituents and antimicrobial activity. The preliminary evaluation of ethanolic extract exhibited appreciable antimicrobial activity on the tested pathogenic bacterial isolates at a concentration of 100mg/g and displayed inhibitory potency (20-22mm) in diameter on the tested bacterial isolates. Phenol and alkaloids was found to be present in the plant parts while highest phenolic constituent was recorded in the leaves extract

A blockchain and deep neural networks-based secure framework for enhanced crop protection

The problem faced by one farmer can also be the problem of some other farmer in other regions. Providing information to farmers and connecting them has always been a challenge. Crowdsourcing and community building are considered as useful solutions to these challenges. However, privacy concerns and inactivity of users can make these models inefficient. To tackle these challenges, we present a cost-efficient and blockchain-based secure framework for building a community of farmers and crowdsourcing the data generated by them to help the farmers’ community. Apart from ensuring privacy and security of data, a revenue model is also incorporated to provide incentives to farmers. These incentives would act as a motivating factor for the farmers to willingly participate in the process. Through integration of a deep neural network-based model to our proposed framework, prediction of any abnormalities present within the crops and their predicted possible solutions would be much more coherent. The simulation results demonstrate that the prediction of plant pathology model is highly accurate