Krishnasamy Gunasekaran

Bio: Krishnasamy Gunasekaran is an academic researcher from University of Madras. The author has contributed to research in topics: Virtual screening & Docking (molecular). The author has an hindex of 9, co-authored 43 publications receiving 221 citations.

Structural modeling, in vitro antiproliferative activity, and the effect of substituents on the DNA fastening and scission actions of heteroleptic copper(II) complexes with terpyridines and naproxen

Abstract: A series of heteroleptic copper(II) complexes of the type [Cu(L1–6)(nap)Cl] (1–6) (L1–6 = 4′-(4-substituted)-2,2′:6′,2′′-terpyridines, nap = naproxen) has been synthesized and characterized. The single crystal analyses of complexes 1 and 6 show distorted octahedral geometry around the copper(II) ion. Structural parameters from the crystallographic and DFT studies are in good agreement with each other. HOMO–LUMO energy levels are constructed and the corresponding theoretical frontier energy gaps are calculated to understand the charge transfer occurring in the molecule, and the lowering of the HOMO–LUMO band gap supports the bioactive properties of the molecule. Electrochemical studies show a one-electron irreversible reduction process in the cathodic potential (Epc) region from −0.75 to −0.82 V. The obtained room-temperature magnetic moment values (1.82–1.93 BM), XRD and EPR spectral data support a distorted octahedral geometry for the copper(II) complexes. The binding studies of complexes 1, 5 and 6 with CT-DNA imply a groove mode of binding, and complex 5 exhibits a higher binding affinity than the other complexes. The binding results are further supported by molecular docking studies. The higher binding propensity of complex 5, containing R5, was proved by computationally derived factors such as chemical potential (μ), chemical hardness (η), electrophilicity (ω) and nuclease-independent chemical shift (NICS). All the complexes display pronounced nuclease activity against supercoiled pBR322 DNA. The in vitro antiproliferative activity of complexes 1, 5 and 6 against human breast cancer cells (MCF-7) was assessed by MTT assay, which shows the potency of 1 and 5, with lower IC50 values than cisplatin and values comparable to doxorubicin. The complexes induce mitochondrial-mediated and caspase-dependent apoptosis with an increase in G0–G1 and subsequent arrest in the S phase in cell cycle evaluation.

Identification of potential PKC inhibitors through pharmacophore designing, 3D-QSAR and molecular dynamics simulations targeting Alzheimer's disease.

Abstract: Protein kinases are ubiquitously expressed as Serine/Threonine kinases, and play a crucial role in cellular activities. Protein kinases have evolved through stringent regulation mechanisms. Protein kinases are also involved in tauopathy, thus are important targets for developing Anti-Alzheimer's disease compounds. Structures with an indole scaffold turned out to be potent new leads. With the aim of developing new inhibitors for human protein kinase C, here we report the generation of four point 3D geometric featured pharmacophore model. In order to identify novel and potent PKCθ inhibitors, the pharmacophore model was screened against 80,000,00 compounds from various chemical databases such as., ZINC, SPEC, ASINEX, which resulted in 127 compound hits, and were taken for molecular docking filters (HTVS, XP docking). After in-depth analysis of binding patterns, induced fit docking (flexible) was employed for six compounds along with the cocrystallized inhibitor. Molecular docking study reveals that compound 6F found to be tight binder at the active site of PKCθ as compared to the cocrystal and has occupancy of 90 percentile. MM-GBSA also confirmed the potency of the compound 6F as better than cocrystal. Molecular dynamics results suggest that compound 6F showed good binding stability of active sites residues similar to cocrystal 7G compound. Present study corroborates the pharmacophore-based virtual screening, and finds the compound 6F as a potent Inhibitor of PKC, having therapeutic potential for Alzheimer's disease. Worldwide, 46.8 million people are believed to be living with Alzheimer's disease. When elderly population increases rapidly and neurodegenerative burden also increases in parallel, we project the findings from this study will be useful for drug developing efforts targeting Alzheimer's disease.

Methods in Enzymology.

Abstract: I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis in the Last Decade

Abstract: Neurodegenerative diseases pose a substantial socioeconomic burden on society. Unfortunately, the aging world population and lack of effective cures foreshadow a negative outlook. Although a large amount of research has been dedicated to elucidating the pathologies of neurodegenerative diseases, their principal causes remain elusive. Metal ion dyshomeostasis, proteopathy, oxidative stress, and neurotransmitter deficiencies are pathological features shared across multiple neurodegenerative disorders. In addition, these factors are proposed to be interrelated upon disease progression. Thus, the development of multifunctional compounds capable of simultaneously interacting with several pathological components has been suggested as a solution to undertake the complex pathologies of neurodegenerative diseases. In this review, we outline and discuss possible therapeutic targets in Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis and molecules, previously designed or discovered as pote...