CoRILISA: A Local Similarity Based Receptor Dependent QSAR Method

Molecular similarity methods have played a crucial role in the success of structure-based and computer-assisted drug design. However, with the exception of CoMSIA, the current approaches for estimating molecular similarity yield a global picture thereby providing limited information about the local spatial molecular features responsible for the variation of activity with the 3D structure. Application of molecular similarity measures, each related to the <i>functional “pieces”</i> of a ligand–receptor complex, is advantageous over a composite molecular similarity alone and will provide more insights to rationally interpret the activity based on the receptor and ligand structural features. Building on the ideas of our previously published methodologiesCoRIA and LISA, we present here a local molecular similarity based receptor dependent QSAR method termed CoRILISA which is a hybrid of the two approaches. The method improves on previous techniques by inclusion of receptor attributes for the calculation and comparison of similarity between molecules. For validation studies, the CoRILISA methodology was applied on three large and diverse data setsglycogen phosphorylase <i>b</i> (GP<i>b</i>), human immunodeficiency virus-1 protease (HIV PR), and cyclin dependent kinase 2 (CDK2) inhibitors. The statistics of the CoRILISA models were benchmarked against the standard CoRIA approach and with other published approaches. The CoRILISA models were found to be significantly better, especially in terms of the predictivity for the test set. CoRILISA is able to identify the thermodynamic properties associated with residues that define the active site and modulate the variation in the activity of the molecules. It is a useful tool in the fragment-based drug discovery approach for ligand activity prediction

Partially Adaptive Cluster Based Routing for Network-on-Chip

As the technology is scaling, reducing wire delays is the major hurdle in increasing communication speed between the cores of System-on-Chip (SoC). Also in today’s technology 50% of silicon area is occupied by interconnects. Efficient use of interconnects is possible due to highly scalable and reliable Network-on-Chip (NoC) communication architecture which has replaced long buses by routers. Routers in NoC make use of intelligent routing algorithms to route the information reliably between the cores irrespective of the topology used. With the help of routing algorithms router optimizes the use of interconnects. Algorithms should provide deadlock free and congestion free routing while ensuring the reachability to destination. This paper presents partially adaptive Cluster based routing referred to as Cluster based routing for regular mesh topology which, (i) Uses cluster approach to reduce the size of routing table. For a 8x8 Mesh there is 76.57% area reduction in routing table. (ii) Provides deadlock free partially adaptive algorithm without use of virtual channels which is achieved by avoiding cyclic paths. (iii) Uses adaptivity to avoid congestion by uniform distribution of traffic between cores

Dibenzyl amine as an ammonia surrogate in the Ugi tetrazoles: Design, synthesis and impactful antioxidant activity

In this study, we develop novel tetrazole compounds based on dibenzyl amine (DBA) and investigate their potential as antioxidants. The aforementioned compounds were synthesised by the Ugi multicomponent reaction, which involved the simultaneous addition of four systems, i.e., DBA, cyclohexyl isocyanide, TMSN3 and aromatic aldehyde in ethanol media under RT. The different isocyanides effect in the progress of the TMSN3 based Ugi reaction was studied. The tetrazoles that were changed with DBA were studied using several techniques, including FTIR, 1H NMR, 13C NMR, and MS. The antioxidant properties of the produced compounds (4a-4j) were subsequently tested in a controlled laboratory setting using the 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical assay. When compared to ascorbic acid, the antioxidant efficacy of all of the produced compounds was high. The obtained results for all prepared compounds were good as an antioxidant in comparison with ascorbic acid. The electron withdrawing effect of the substituents (halogens and nitro groups) on the aromatic side enhanced the antioxidant activity of the newly derived motifs. Their molecular docking investigation with the myeloperoxidase (MPO) enzyme revealed a strong relationship between their binding modalities and the antioxidant properties they displayed

Synthesis and 3D-QSAR study of 1,4-dihydropyridine derivatives as MDR cancer reverters

A series of symmetrical and unsymmetrical 1,4-dihydropyridines were synthesized by a rapid, single pot microwave irradiation (MWI) based protocol along with conventional approach and characterized by NMR, IR and mass spectroscopic techniques. The compounds were evaluated for their tumor cell cytotoxicity in HL-60 tumor cells. A 3D-QSAR study using CoMFA and CoMSIA was carried out to decipher the factors governing MDR reversing ability in cancer. The resulting contour maps derived by the best 3D-QSAR models provide a good insight into the molecular features relevant to the biological activity in this series of analogs. 3D contour maps as a result of 3D-QSAR were utilized to identify some novel features that can be incorporated into the 1,4-dihydropyridine framework to enhance the activity

4-Thiazolidinone Based 5-Arylidene Hybrids: Design, Synthesis, Antimicrobial Activity, and Molecular Docking Studies

In recent years, the most pressing challenge in drug development has been the fight against bacterial drug resistance. Microbes have developed resistance against the present classes of antibiotics, necessitating the development of new antibiotics capable of replacing less effective drugs commercially accessible in the market. In order to achieve this, a straightforward technique for the synthesis of 4-thiazolidinone-based pyrazole-pyridine hybrids was designed (5a–o). The hybrids were characterized using spectroscopic techniques and tested for antimicrobial efficacy against a variety of bacterial and fungal species. The MIC value of compounds 5d, 5f, 5j, 5 l, 5 m, and 5o against tested bacterial strains was 62.5 μg/mL. Compound 5i showed a MIC value of 250 μg/mL against Candida albicans, which is twice the activity of the standard drug. Furthermore, to rationalize the antimicrobial finding and to gain an insight into the plausible mechanism of action, molecular docking study was performed against microbial DNA gyrase. A very significant correlation obtained between the in silico binding affinity and the antimicrobial activity could set an excellent platform for structure based drug design.</p