Design, Synthesis and Screening of Pyrazole Linked Thiazolidinones, Oxazepines and Benzoxazepines As Pf-Enr And E.Coli Fabi Inhibitors

INTRODUCTION:Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Drug design for the knowledge of the three-dimensional structure of the biomolecular target is equant but not necessarily relies on computer modelling techniques. This type of modelling is sometimes referred to as computer-aided drug design.PURPOSE AND PLAN OF WORK:The prime motivation of the present work is to design a drug in such a way that it can be used clinically to treat the disease. Drug discovery tools have been utilized now in designing new molecular entities which are safe and effective without consuming much of the research hours. Recent literatures shows that search of new drugs are now focussed on design of drugs as inhibitors of enzyme targets. Enoyl ACP reductase is such a potential drug target in the development of new antimicrobial agents. From the literature and virtual screening technique Triclosan analogues, pyrazole, thiazolidinone, oxazepine, etc., possess promising enoyl ACP reductase inhibiting action on both Plasmodium falciparum and Escherichia coli. Based on these reports an attempt was made here to design and develop new antiplasmodial and antibacterial agents by utilizing computational tools. The primary objective of the present work is to identify and synthesize pyrazole linked thiazolidinone, oxazepine and benzoxazepine as promising antiplasmodial and antibacterial agents by the inhibition of enoyl ACP reductase enzyme.SUMMARY:The present work was focused on the design, docking, synthesis and evaluation of antimalarial and antibacterial activity of Pyrazolyl linked thiazolidinone, oxazepine and benzoxazepine series as possible Enoyl ACP reductase inhibitors. Phase I - In-silico studies Selection of the target The enzyme involved in the fatty acid elongation of Plasmodium falciparum and Escherichia coli ie., Enoyl ACP reductase was selected as the drug target of the study. The corresponding enzyme were obtained from the protein data bank and their accession codes were 1VRW (PfENR) and 1C14 (E.coli Fab1). Selection of lead by virtual screening Virtual screening was performed by iGEMDOCK v.2. Forty nine hits were obtained from ZINC database, from which pyrazole, thiazolidinone and oxazepine were selected as the lead for inhibiting PfENR and E.coli FabI enzymes. Lead optimization The thirty modified ligands 2a-j, 3a-j and 4a-j were subjected to in-silico lead optimization. The ligands were optimized for evaluating oral bioavailability by utilizing the Molinspiration server. Lead optimization revealed that all the thirty selected derivatives possess good drug likeness score. Docking The optimized leads were subjected to docking studies using Autodock4.2 and the interactions of the derivatives with active sites of the enzymes were studied. The derivatives were subjected to interactions with PfENR and E.coli FabI. Triclosan was used as the standard ligand.CONCLUSION:The present study establishes that computational tools help in minimizing the tedious process of drug discovery and delivers new drug candidate more quickly. Virtual screening was utilized for filtering the compounds and selecting the lead compounds. The drug likeness score established the compounds to be pharmacokinetically active. The binding energy obtained from docking study further confirmed the possibility of the affinity of the selected leads towards the enzyme, enoyl ACP reductase from Plasmodium falciparum and Escherichia coli. Using the schemes various pyrazolyl linked thiazolidinone, oxazepine and benzoxazepine were synthesized with good yield. Structure of the synthesized compounds were confirmed by Melting point, TLC, UV, NMR and MASS spectra. The compounds were screened for antimalarial and antibacterial activity. Thus the present study depicts that the utilization of computer aided drug design is an efficient tool in predicting the effectiveness of a series of compounds under study and thus can result in the design of potent antimalarial and antibacterial agents

PHARMACOLOGICAL PROPERTIES OF LEONOTIS NEPETIFOLIA (L) R.BR - A SHORT REVIEW

Leonotis nepetifolia (L) R.Br commonly known as Lion’s ear, has number of therapeutic properties and is also known as Christmas candlestic. The genus Leonotis has 12 species widely distributed in Pan Tropics and is represented by one species, Leonotis nepetifolia in India. It belongs to family Lamiaceae. Leonotis nepetifolia is an economically important medicinal plant of repute in Indian traditional systems of medicine such as Ayurveda, Unani and Siddha. The Ayurvedic name of the plant is Granthiparni, while the trade name is Barchi Buti. It has many therapeutic properties and proved in Madagascar, Brazil, Canada, Kenya and many African Countries to treat diseases, rheumatism, dysmenorrhoea, bronchial asthma, fever, diarrhoea influenza and malaria and is also an analgesic. The decoction of the leaves is used to treat coughs, burns and skin ailments. The whole plant is used for menstrual pain and unspecified female complaints. This plant exhibited various pharmacological activities such as antioxidant activity, antidiabetic, anticancer, anti-inflammatory, anticonvulsant, wound healing, hepatoprotective activity and antimicrobial activities. Phytochemical examination of this plant indicated the presence of alkaloids (leonurine and stachydrene), iridoid glycoside (leonuride), iridoid glycosides (leonurin and leonuridine), diterpenoids (leocardin), flavonoids (rutin, quercetin, hyperoside, apigenin), volatile oil, tannins and vitamin A. Leonotis nepetifolia is highly therapeutic and is used in various Ayurvedic formulations. This article briefly reviews the pharmacological and various therapeutic aspect of Leonotis nepetifolia

Prevalence of enteropathogens and their antibiotic sensitivity pattern in puppies with hemorrhagic gastroenteritis

Aim: Hemorrhagic gastroenteritis (HGE) ranging from mild to severe forms is commonly encountered in puppies. The aim of the study was to identify the prevalence of common enteropathogens and the antibiotic sensitivity pattern in puppies reported with HGE. Materials and Methods: The canine HGE activity index, with little modification, was adopted to identify Grade III/ severely affected puppies below 6 months of age. Fecal polymerase chain reaction (PCR) assay was employed to screen and compare the enteropathogens in puppies with hemorrhagic diarrhea and healthy control. Results: Canine parvovirus 2b was identified in 90.3% of the diarrheic and 10% of the non-diarrheic healthy puppies. Clostridium difficile was identified in all the diarrheic puppies and in 80% of the healthy puppies. Among the diarrheic puppies, 17.7% were positive for Clostridium perfringens enterotoxin, 9.7% were positive for C. perfringens alpha toxin, 6.4% were positive for Escherichia coli shiga toxin, 6.4% were positive for E. coli enterotoxin (LT), and 3.2% were positive for canine distemper virus. Whereas, none of the healthy puppies were positive for these bacteria and toxins. Fecal antibiotic sensitivity test pattern revealed gentamicin to be sensitive in 95% of the cases, azithromycin in 50%, enrofloxacin in 25%, cefotaxime in 20%, and tetracycline in 5% of the cases. Conclusion: Parvoviral enteritis is predominant among puppies. Yet, bacteria and their toxins also play an important role in HGE. Gentamicin has higher sensitivity against the enteropathogens associated with the condition

Forensic video solution using facial feature‐based synoptic Video Footage Record

Person specific identification is an important problem in computer vision. However, forensic video analysis is the tool in surveillance applications, such as a specific person Video Footage Record can be used to help personalised monitoring. This study proposes a solution to identify the specific person very quickly through offline which will be valuable to analyse the incident/crime earlier. The main idea of this study is to reduce the enormous volume of video data by using an object‐based video synopsis. After that, Viola–Jones face detection, deformable part based models are used to detect the face attributes. Subsequently, histogram of oriented gradients and oriented centre symmetric local binary pattern features are extracted. Support vector machine classifier is used to classify the weak and strong features. These strong features are used to recognise the person. The algorithm works well even in complicated situations such as expression changes, pose, illumination variations and even if the face is partially as well as fully occluded in few frames. The advantage of synoptic video helps to recognise the person who is not occluded in some other frames. Experimental results on benchmark and real time datasets demonstrate the effectiveness of the proposed algorithm