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Antibacterial, antifungal and anticonvulsant evaluation of novel newly synthesized 1-[2-(1H-tetrazol-5-yl)ethyl]-1H-benzo[d][1, 2,3]triazoles

Rajasekaran A, Murugesan S, AnandaRajagopal K

Arch Pharm Res, 2006 Jul;29(7):535-40.
PMID: 16903071

Several novel 1-[2-(1H-tetrazol-5-yl) ethyl]-1H-benzo[d][1,2,3]triazoles (3a-h) have been synthesized by the condensation of 1-[2-(1H-tetrazol-5-yl)-ethyl]-1H-benzotriazole (2) and appropriate acid chlorides. 1-[2-(1H-tetrazol-5-yl)-ethyl]-1H-benzotriazole (2) was synthesized by reacting 3-(1H-benzo[d][1,2,3]triazol-1-yl)propanenitrile with sodium azide and ammonium chloride in the presence of dimethylformamide. The synthesized compounds were characterized by IR and PMR analysis. The titled compounds were evaluated for their in-vitro antibacterial and antifungal activity by the cup plate method and anticonvulsant activity evaluated by the maximal electroshock induced convulsion method in mice. All synthesized compounds exhibited moderate antibacterial activity against Bacillus subtilis and moderate antifungal activity against Candida albicans. Compounds 5-(2-(1H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H-tetrazol-1-yl)(4-aminophenyl)methanone 3d and 5-(2-(1 H-benzo[d][1,2,3]triazo-1-yl)ethyl)-1H-tetrazol-1-yl)(2-aminophenyl)methanone 3e elicited excellent anticonvulsant activity.
Fulltext Biomaterials in cardiovascular research: applications and clinical implications

Jaganathan SK, Supriyanto E, Murugesan S, Balaji A, Asokan MK

Biomed Res Int, 2014;2014:459465.
PMID: 24895577 DOI: 10.1155/2014/459465

Cardiovascular biomaterials (CB) dominate the category of biomaterials based on the demand and investments in this field. This review article classifies the CB into three major classes, namely, metals, polymers, and biological materials and collates the information about the CB. Blood compatibility is one of the major criteria which limit the use of biomaterials for cardiovascular application. Several key players are associated with blood compatibility and they are discussed in this paper. To enhance the compatibility of the CB, several surface modification strategies were in use currently. Some recent applications of surface modification technology on the materials for cardiovascular devices were also discussed for better understanding. Finally, the current trend of the CB, endothelization of the cardiac implants and utilization of induced human pluripotent stem cells (ihPSCs), is also presented in this review. The field of CB is growing constantly and many new investigators and researchers are developing interest in this domain. This review will serve as a one stop arrangement to quickly grasp the basic research in the field of CB.
Fulltext Enhanced blood compatibility of metallocene polyethylene subjected to hydrochloric acid treatment for cardiovascular implants

Jaganathan SK, Mohandas H, Sivakumar G, Kasi P, Sudheer T, Avineri Veetil S, et al.

Biomed Res Int, 2014;2014:963149.
PMID: 24955370 DOI: 10.1155/2014/963149

Blood compatibility of metallocene polyethylene (mPE) was investigated after modifying the surface using hydrochloric acid. Contact angle of the mPE exposed to HCl poses a decrease in its value which indicates increasing wettability and better blood compatibility. Surface of mPE analyzed by using FTIR revealed no significant changes in its functional groups after treatment. Furthermore, scanning electron microscope images supported the increasing wettability through the modifications like pit formations and etching on the acid rendered surface. To evaluate the effect of acid treatment on the coagulation cascade, prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. Both PT and APTT were delayed significantly (P < 0.05) after 60 min exposure implying improved blood compatibility of the surfaces. Hemolysis assay of the treated surface showed a remarkable decrease in the percentage of lysis of red blood cells when compared with untreated surface. Moreover, platelet adhesion assay demonstrated that HCl exposed surfaces deter the attachment of platelets and thereby reduce the chances of activation of blood coagulation cascade. These results confirmed the enhanced blood compatibility of mPE after HCl exposure which can be utilized for cardiovascular implants like artificial vascular prostheses, implants, and various blood contacting devices.
Fulltext Multifaceted prospects of nanocomposites for cardiovascular grafts and stents

Vellayappan MV, Balaji A, Subramanian AP, John AA, Jaganathan SK, Murugesan S, et al.

Int J Nanomedicine, 2015;10:2785-803.
PMID: 25897223 DOI: 10.2147/IJN.S80121

Cardiovascular disease is the leading cause of death across the globe. The use of synthetic materials is indispensable in the treatment of cardiovascular disease. Major drawbacks related to the use of biomaterials are their mechanical properties and biocompatibility, and these have to be circumvented before promoting the material to the market or clinical setting. Revolutionary advancements in nanotechnology have introduced a novel class of materials called nanocomposites which have superior properties for biomedical applications. Recently, there has been a widespread recognition of the nanocomposites utilizing polyhedral oligomeric silsesquioxane, bacterial cellulose, silk fibroin, iron oxide magnetic nanoparticles, and carbon nanotubes in cardiovascular grafts and stents. The unique characteristics of these nanocomposites have led to the development of a wide range of nanostructured copolymers with appreciably enhanced properties, such as improved mechanical, chemical, and physical characteristics suitable for cardiovascular implants. The incorporation of advanced nanocomposite materials in cardiovascular grafts and stents improves hemocompatibility, enhances antithrombogenicity, improves mechanical and surface properties, and decreases the microbial response to the cardiovascular implants. A thorough attempt is made to summarize the various applications of nanocomposites for cardiovascular graft and stent applications. This review will highlight the recent advances in nanocomposites and also address the need of future research in promoting nanocomposites as plausible candidates in a campaign against cardiovascular disease.
Search for new therapeutics against HIV-1 via dual inhibition of RNase H and integrase: current status and future challenges

Kharkwal H, Kumar BK, Murugesan S, Singhvi G, Avasthi P, Goyal A, et al.

Future Med Chem, 2021 02;13(3):269-286.
PMID: 33399497 DOI: 10.4155/fmc-2020-0257

Reverse transcriptase and integrase are key enzymes that play a pivotal role in HIV-1 viral maturation and replication. Reverse transcriptase consists of two active sites: RNA-dependent DNA polymerase and RNase H. The catalytic domains of integrase and RNase H share striking similarity, comprising two aspartates and one glutamate residue, also known as the catalytic DDE triad, and a Mg2+ pair. The simultaneous inhibition of reverse transcriptase and integrase can be a rational drug discovery approach for combating the emerging drug resistance problem. In the present review, the dual inhibition of RNase H and integrase is systematically discussed, including rationality of design, journey of development, advancement and future perspective.
Solvent-free benzylic oxidation of aromatics over Cu(II)-containing propylsalicylaldimine anchored on the surface of mesoporous silica catalysts

Selvaraj M, Assiri MA, Rokhum SL, Manjunatha C, Appaturi JN, Murugesan S, et al.

Dalton Trans, 2021 Nov 02;50(42):15118-15128.
PMID: 34612261 DOI: 10.1039/d1dt01760h

A sustainable method was used to produce aromatic ketones by the solvent-free benzylic oxidation of aromatics over mesoporous Cu(II)-containing propylsalicylaldimine anchored on the surface of Santa Barbara Amorphous type material-15 (CPSA-SBA-15) catalysts. For comparison, mesoporous Cu(II)-containing propylsalicylaldimine anchored with Mobil Composition of Matter-41 (CPSA-MCM-41) was assessed for these reactions under similar reaction conditions. The washed CPSA-SBA-15(0.2) (W-CPSA-SBA-15(0.2)) catalyst was prepared using an easy chemical method for the complete removal of non-framework CuO nanoparticle species on the surface of pristine CPSA-SBA-15(0.2) (p-CPSA-SBA-15(0.2) prepared with 0.2 wt% of Cu, and its catalytic activity was evaluated with different reaction parameters, oxidants and solvents. In order to confirm the catalytic stability, the recyclability was assessed, and the performance of hot-filtration experiments was also evaluated. All the catalysts used for these catalytic reactions were characterized using many instrumental techniques to pinpoint the mesoporous nature and active sites of the catalysts. The proposed reaction mechanism has been well documented on the basis of catalytic results obtained for solvent-free oxidation of aromatics. Based on the catalytic results, we found that W-CPSA-SBA-15(0.2) is a very ecofriendly catalyst with exceptional catalytic activity.
Synthesis, anti-acetylcholinesterase evaluation, molecular docking and molecular dynamics simulation of novel Psoralen derivatives

Hasan AH, Mohamed Yusof FS, Kamarudin NA, Murugesan S, Shakya S, Jamalis J

Curr Org Synth, 2023 Mar 28.
PMID: 36998126 DOI: 10.2174/1570179420666230328121554

INTRODUCTION: Seven new psoralen derivatives were synthesised by carbodiimide coupling to active carboxylic acid to amide formation in mild reaction conditions.
METHODS: The psoralen derivatives were produced through the condensation of seven different types of amine groups consisting of electron withdrawing groups and electron donating groups.
RESULTS: All the synthesised compounds were obtained with moderate to high yields. Structural characterization using ATR-FTIR, 1H NMR, 13C NMR, and HRMS has confirmed their structure. Moreover, in silico evaluation of the psoralen derivatives against the AChE enzyme was performed, and acetylcholinesterase inhibitory activity of psoralen derivatives was also conducted.
CONCLUSION: Results from molecular docking show the potential of compound 12e as AChE inhibitors due to its highest binding energy value. It was further supported by the anti-acetylcholinesterase activity of compound 12e, which has 91.69% inhibition, comparable to galantamine (94.12%). Furthermore, 100 ns run molecular dynamics (MD) simulation was used to refine docking results.
Tangible nanocomposites with diverse properties for heart valve application

Vellayappan MV, Balaji A, Subramanian AP, John AA, Jaganathan SK, Murugesan S, et al.

Sci Technol Adv Mater, 2015 Jun;16(3):033504.
PMID: 27877785

Cardiovascular disease claims millions of lives every year throughout the world. Biomaterials are used widely for the treatment of this fatal disease. With the advent of nanotechnology, the use of nanocomposites has become almost inevitable in the field of biomaterials. The versatile properties of nanocomposites, such as improved durability and biocompatibility, make them an ideal choice for various biomedical applications. Among the various nanocomposites, polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane, bacterial cellulose with polyvinyl alcohol, carbon nanotubes, graphene oxide and nano-hydroxyapatite nanocomposites have gained popularity as putative choices for biomaterials in cardiovascular applications owing to their superior properties. In this review, various studies performed utilizing these nanocomposites for improving the mechanical strength, anti-calcification potential and hemocompatibility of heart valves are reviewed and summarized. The primary motive of this work is to shed light on the emerging nanocomposites for heart valve applications. Furthermore, we aim to promote the prospects of these nanocomposites in the campaign against cardiovascular diseases.
Fulltext Potential inhibitory activity of phytoconstituents against black fungus: In silico ADMET, molecular docking and MD simulation studies

Hamaamin Hussen N, Hameed Hasan A, Jamalis J, Shakya S, Chander S, Kharkwal H, et al.

Comput Toxicol, 2022 Nov;24:100247.
PMID: 36193218 DOI: 10.1016/j.comtox.2022.100247

Mucormycosis or "black fungus" has been currently observed in India, as a secondary infection in COVID-19 infected patients in the post-COVID-stage. Fungus is an uncommon opportunistic infection that affects people who have a weak immune system. In this study, 158 antifungal phytochemicals were screened using molecular docking against glucoamylase enzyme of Rhizopus oryzae to identify potential inhibitors. The docking scores of the selected phytochemicals were compared with Isomaltotriose as a positive control. Most of the compounds showed lower binding energy values than Isomaltotriose (-6.4 kcal/mol). Computational studies also revealed the strongest binding affinity of the screened phytochemicals was Dioscin (-9.4 kcal/mol). Furthermore, the binding interactions of the top ten potential phytochemicals were elucidated and further analyzed. In-silico ADME and toxicity prediction were also evaluated using SwissADME and admetSAR online servers. Compounds Piscisoflavone C, 8-O-methylaverufin and Punicalagin exhibited positive results with the Lipinski filter and drug-likeness and showed mild to moderate of toxicity. Molecular dynamics (MD) simulation (at 300 K for 100 ns) was also employed to the docked ligand-target complex to explore the stability of ligand-target complex, improve docking results, and analyze the molecular mechanisms of protein-target interactions.
Fulltext Evaluation of the Diagnostic and Prognostic Accuracy of Artificial Intelligence in Endodontic Dentistry: A Comprehensive Review of Literature

Karobari MI, Adil AH, Basheer SN, Murugesan S, Savadamoorthi KS, Mustafa M, et al.

Comput Math Methods Med, 2023;2023:7049360.
PMID: 36761829 DOI: 10.1155/2023/7049360

AIM: This comprehensive review is aimed at evaluating the diagnostic and prognostic accuracy of artificial intelligence in endodontic dentistry.
INTRODUCTION: Artificial intelligence (AI) is a relatively new technology that has widespread use in dentistry. The AI technologies have primarily been used in dentistry to diagnose dental diseases, plan treatment, make clinical decisions, and predict the prognosis. AI models like convolutional neural networks (CNN) and artificial neural networks (ANN) have been used in endodontics to study root canal system anatomy, determine working length measurements, detect periapical lesions and root fractures, predict the success of retreatment procedures, and predict the viability of dental pulp stem cells. Methodology. The literature was searched in electronic databases such as Google Scholar, Medline, PubMed, Embase, Web of Science, and Scopus, published over the last four decades (January 1980 to September 15, 2021) by using keywords such as artificial intelligence, machine learning, deep learning, application, endodontics, and dentistry.
RESULTS: The preliminary search yielded 2560 articles relevant enough to the paper's purpose. A total of 88 articles met the eligibility criteria. The majority of research on AI application in endodontics has concentrated on tracing apical foramen, verifying the working length, projection of periapical pathologies, root morphologies, and retreatment predictions and discovering the vertical root fractures.
CONCLUSION: In endodontics, AI displayed accuracy in terms of diagnostic and prognostic evaluations. The use of AI can help enhance the treatment plan, which in turn can lead to an increase in the success rate of endodontic treatment outcomes. The AI is used extensively in endodontics and could help in clinical applications, such as detecting root fractures, periapical pathologies, determining working length, tracing apical foramen, the morphology of root, and disease prediction.
Fulltext Recent Progress in Synthesis, POM Analyses and SAR of Coumarin-Hybrids as Potential Anti-HIV Agents-A Mini Review

Suleiman M, Almalki FA, Ben Hadda T, Kawsar SMA, Chander S, Murugesan S, et al.

Pharmaceuticals (Basel), 2023 Oct 31;16(11).
PMID: 38004404 DOI: 10.3390/ph16111538

The human immunodeficiency virus (HIV) is the primary cause of acquired immune deficiency syndrome (AIDS), one of the deadliest pandemic diseases. Various mechanisms and procedures have been pursued to synthesise several anti-HIV agents, but due to the severe side effects and multidrug resistance spawning from the treatment of HIV/AIDS using highly active retroviral therapy (HAART), it has become imperative to design and synthesise novel anti-HIV agents. Literature has shown that natural sources, particularly the plant kingdom, can release important metabolites that have several biological, mechanistic and structural representations similar to chemically synthesised compounds. Certainly, compounds from natural and ethnomedicinal sources have proven to be effective in the management of HIV/AIDS with low toxicity, fewer side effects and affordability. From plants, fungi and bacteria, coumarin can be obtained, which is a secondary metabolite and is well known for its actions in different stages of the HIV replication cycle: protease, integrase and reverse transcriptase (RT) inhibition, cell membrane fusion and viral host attachment. These, among other reasons, are why coumarin moieties will be the basis of a good building block for the development of potent anti-HIV agents. This review aims to outline the synthetic pathways, structure-activity relationship (SAR) and POM analyses of coumarin hybrids with anti-HIV activity, detailing articles published between 2000 and 2023.
Design, synthesis, anti-acetylcholinesterase evaluation and molecular modelling studies of novel coumarin-chalcone hybrids

Hasan AH, Shakya S, Hussain FHS, Murugesan S, Chander S, Pratama MRF, et al.

J Biomol Struct Dyn, 2023;41(21):11450-11462.
PMID: 36591704 DOI: 10.1080/07391102.2022.2162583

The major enzyme responsible for the hydrolytic breakdown of the neurotransmitter acetylcholine (ACh) is acetylcholinesterase (AChE). Acetylcholinesterase inhibitors (AChEIs) are the most prescribed class of medications for the treatment of Alzheimer's disease (AD) and dementia. The limitations of available therapy, like side effects, drug tolerance, and inefficacy in halting disease progression, drive the need for better, more efficacious, and safer drugs. In this study, a series of fourteen novel chalcone-coumarin derivatives (8a-n) were designed, synthesized and characterized by spectral techniques like FT-IR, NMR, and HR-MS. Subsequently, the synthesized compounds were tested for their ability to inhibit acetylcholinesterase (AChE) activity by Ellman's method. All tested compounds showed AChE inhibition with IC50 value ranging from 0.201 ± 0.008 to 1.047 ± 0.043 μM. Hybrid 8d having chloro substitution on ring-B of the chalcone scaffold showed relatively better potency, with IC50 value of 0.201 ± 0.008 μM compared to other members of the series. The reference drug, galantamine, exhibited an IC50 at 1.142 ± 0.027 μM. Computational studies revealed that designed compounds bind to the peripheral anionic site (PAS), the catalytic active site (CAS), and the mid-gorge site of AChE. Putative binding modes, ligand-enzyme interactions, and stability of the best active compound are studied using molecular docking, followed by molecular dynamics (MD) simulations. The cytotoxicity of the synthesised derivatives was determined using the MTT test at three concentrations (100 g/mL, 500 g/mL, and 1 mg/mL). None of the chemicals had a significant effect on the body at the highest dose of 1 mg/mL.Communicated by Ramaswamy H. Sarma.
Synthesis, biological evaluation and molecular modeling studies of modulated benzyloxychalcones as potential acetylcholinesterase inhibitors

Abdalla Ali A, Mhamad SA, Hasan AH, Ahmad I, Abdullah SA, Jamil S, et al.

J Biomol Struct Dyn, 2024 Apr;42(7):3604-3615.
PMID: 37293930 DOI: 10.1080/07391102.2023.2220032

Acetylcholinesterase inhibitors (AChEIs) have become a significant target in the search for an efficient treatment of Alzheimer's disease. Chalcone-based compounds display a strong potency to hinder AChE. So, this study focused on the synthesis of a series of new chalcone derivatives with anti-cholinesterase potential and their structures were characterized based on spectroscopic methods including IR, 1H NMR, 13C NMR and HRMS. Chalcone derivatives were screened against AChE. Most of them exhibited potent inhibitory activity against AChE. Compound 11i showed the most potent activity toward acetylcholinesterase compared to the positive compound, Galantamine. Docking studies into the active site of the acetylcholinesterase enzyme ravealed the significant docking score of the synthesized compounds with docking score of -7.959 to -9.277 kcal/mol when compared to the co-crystallized ligand, Donepezil (-10.567 kcal/mol). The interaction's stability was further assessed using a conventional atomistic 100 ns dynamics simulation study, which revealed the conformational stability of representative compound 11i in the cavity of the acetylcholinesterase enzyme.Communicated by Ramaswamy H. Sarma.
Novel thiophene Chalcones-Coumarin as acetylcholinesterase inhibitors: Design, synthesis, biological evaluation, molecular docking, ADMET prediction and molecular dynamics simulation

Hasan AH, Murugesan S, Amran SI, Chander S, Alanazi MM, Hadda TB, et al.

Bioorg Chem, 2022 02;119:105572.
PMID: 34971946 DOI: 10.1016/j.bioorg.2021.105572

A series of around eight novel chalcone based coumarin derivatives (23a-h) was designed, subjected to in-silico ADMET prediction, synthesized, characterized by IR, NMR, Mass analytical techniques and evaluated as acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer's disease (AD). The results of predicted ADMET study demonstrated the drug-likeness properties of the titled compounds with developmental challenges in lipophilicity and solubility parameters. The in vitro assessment of the synthesized compounds revealed that all of them showed significant activity (IC50 ranging from 0.42 to 1.296 µM) towards AChE compared to the standard drug, galantamine (IC50 = 1.142 ± 0.027 µM). Among these, compound 23e displayed the most potent inhibitory activity with IC50 value of 0.42 ± 0.019 µM. Cytotoxicity of all compounds was tested on normal human hepatic (THLE-2) cell lines at three different concentrations using the MTT assay, in which none of the compound showed significant toxicity at the highest concentration of 1000 µg/ml compared to the control group. Based on the docking study against AChE, the most active derivative 23e was orientated towards the active site and occupied both catalytic anionic site (CAS) and peripheral anionic site (PAS) of the target enzyme. In-silico studies revealed tested showed better inhibition activity of AChE compared to Butyrylcholinesterase (BuChE). Molecular dynamics simulation explored the stability and dynamic behavior of 23e- AChE complex.

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