In silico and in vitro evaluation of newly synthesized pyrazolo-pyridine fused tetrazolo-pyrimidines derivatives as potential anticancer and antimicrobial agents.

Diversely functionalized pyrazolo-pyridine fused tetrazolo-pyrimidines 10aa-am and 10ba-bn were successfully synthesized via a catalyst-free synthetic protocol with moderate to very good yields. The compounds were evaluated for cytotoxicity against MCF-7 and HEK-293 cells using MTT assay. Among the tested compounds, 10ab (IC50- 23.83 µM) and 10ah (IC50- 23.30 µM) demonstrated the highest potency against MCF-7 cells, while 10bc (IC50- 14.46 µM) and 10bh (IC50- 2.53 µM) exhibited excellent cytotoxicity against HEK-293 cells. Additionally, antibacterial screening was performed against three Gram-negative bacteria (E. coli, P. aeruginosa, and S. enterica) and three Gram-positive bacteria (S. aureus, B. megaterium, and B. subtilis) using broth dilution method, while antifungal activity was assessed against three fungal strains (A. niger, Penicillium, and S. cerevisiae) using agar well diffusion method. In antimicrobial screening, the majority of the compounds demonstrated significant antibacterial efficacy compared to antifungal activity. We also conducted comprehensive computational studies, including DFT calculations, molecular docking and dynamics, and drug-likeness assessments. In the DFT study, compounds 10ac and 10bc displayed stable conformations, indicating their potential for higher therapeutic activity. Molecular docking analyses revealed compelling interactions, with compound 10ah demonstrating docking score -7.42 kcal/mol against catalytical domain PARP1 (PDB ID: 7KK4) and 10bh exhibiting a best docking score -10.77 kcal/mol against human corticotropin-releasing factor receptor 1 (PDB ID: 4Z9G). A 100 ns molecular dynamics (MD) simulation study of compounds 10ah and 10bh revealed the stable conformation and binding energy in a stimulating environment. In drug-likeness assessments, both the compounds 10ah and 10bh adhere all the established guidelines.Communicated by Ramaswamy H. Sarma.

Computational investigation of natural compounds as potential main protease (Mpro) inhibitors for SARS-CoV-2 virus.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is significantly impacting human lives, overburdening the healthcare system and weakening global economies. Plant-derived natural compounds are being largely tested for their efficacy against COVID-19 targets to combat SARS-CoV-2 infection. The SARS-CoV-2 Main protease (Mpro) is considered an appealing target because of its role in replication in host cells. We curated a set of 7809 natural compounds by combining the collections of five databases viz Dr Duke's Phytochemical and Ethnobotanical database, IMPPAT, PhytoHub, AromaDb and Zinc. We applied a rigorous computational approach to identify lead molecules from our curated compound set using docking, dynamic simulations, the free energy of binding and DFT calculations. Theaflavin and ginkgetin have emerged as better molecules with a similar inhibition profile in both SARS-CoV-2 and Omicron variants.

In Silico Studies and Design of Scrupulous Novel Sensor for Nitro Aromatics Compounds and Metal Ions Detection.

A Novel calix[4]pyrrole system bearing carboxylic acid functionality [ABuCP] has been synthesized and its interaction towards various nitroaromatics compounds [NACs] were investigated. ABuCP showed significant color change with 1,3-dinitro benzene (1,3-DNB) in comparison to the solution of other nitroaromatic compounds such as 2,3-dinitro toluene (2,3-DNT), 2,4-dinitro toluene (2,4-DNT), 2,6-dinitro toluene (2,6-DNT), 4-NBB (4-nitrobenzyl bromide) and 4-nitro toluene (4-NT). The ABuCP-1,3-DNB complex produces a red shift in absorption spectra based on charge transfer mediated recognition. Additionally, the density functional theory calculation confirmed the possible mechanism for the binding of 1,3-DNB as a guest is well supported by the calculation of other parameters such as hardness, stabilization energy, softness, electrophilicity index and chemical potential. The TDDFT calculation facilitates the understanding of the proper binding mechanism in reference to experimental results. Additionally we have also developed its derivative which acts as a new fluorescent sensor which can selectively recognize Sr(II) ions. In this view its aminoanthraquinone derivative of calix[4]pyrrole i.e. ABuCPTAA is synthesized which also results in generation of high fluorescence capability sensor.

Functionalized Silver Nanoparticles as Colorimetric and Fluorimetric Sensor for Environmentally Toxic Mercury Ions: An Overview.

Nanoscience is a multifaceted field which encompasses metal nanoparticles (MNPs) having novel and size-related optical properties significantly different from the bulk level as well as at the atomic level. Amongst noble MNPs, the silver nanoparticles (AgNPs) have unique properties for metal interaction. Presently, there have been expedite reports which are taken under the review in virtue of sensing the mercury ions in aqueous media. Mercury dissemination in various forms contaminates the ecosystem. Globally mercury is ranked as the most toxic element and an urgent threat to humans since it causes major health issues. Employing MNPs, especially AgNPs for the detection of mercury ions is the economic, handy and apt method in contrast to time-consuming methods that use expensive instrumentations. The review highlights a study of colorimetric and fluorimetric detection of the level of Hg (II) ions in aqueous media selectively with high sensitivity in different courses of conditions using AgNPs synthesized by various approaches. Graphical abstract.

An oxacalix[4]arene derived dual sensing fluorescent probe for the detection of As(v) and Cr(vi) oxyanions in aqueous media.

An oxacalix[4]arene-Ce(iii) complex viz. L-Ce(III) has been introduced for the selective detection of As(v) and Cr(vi) oxyanions in aqueous medium. The binding mode of L-Ce(III) + AsO43-/CrO42- was completely investigated with fluorometric titration, time resolve fluorescent decay and FTIR analyses. Photoinduced electron transfer (PET) and chelation-enhanced fluorescence (CHEF) play an important role in the sensing of these oxyanions. The characteristic fluorescence of the L-Ce(III) complex has been quenched by AsO43- and CrO42- through cascading the ligating sites. Cyclic voltammetry (CV) experiments with various scan rates suggest that the electrochemical processes on the electrodes were controlled by diffusion. Both the analytes exhibit a lower limit of detection (LOD) below their standard EPA permissible limits. Moreover, the probe successfully detects the oxyanions in environmental real samples with excellent recovery ranging from 97 to 101%.

Cardiotonic steroids as potential Na+/K+-ATPase inhibitors - a computational study.

Cardiotonic steroids (CTS) are steroidal drugs, processed from the seeds and dried leaves of the genus Digitalis as well as from the skin and parotid gland of amphibians. The most commonly known CTS are ouabain, digoxin, digoxigenin and bufalin. CTS can be used for safer medication of congestive heart failure and other related conditions due to promising pharmacological and medicinal properties. Ouabain isolated from plants is widely utilized in in vitro studies to specifically block the sodium potassium (Na+/K+-ATPase) pump. For checking, whether ouabain derivatives are robust inhibitors of Na+/K+-ATPase pump, molecular docking simulation was performed between ouabain and its derivatives using YASARA software. The docking energy falls within the range of 8.470 kcal/mol to 7.234 kcal/mol, in which digoxigenin was found to be the potential ligand with the best docking energy of 8.470 kcal/mol. Furthermore, pharmacophore modeling was applied to decipher the electronic features of CTS. Molecular dynamics simulation was also employed to determine the conformational properties of Na+/K+-ATPase-ouabain and Na+/K+-ATPase-digoxigenin complexes with the plausible structural integrity through conformational ensembles for 100 ns which promoted digoxigenin as the most promising CTS for treating conditions of congestive heart failure patients.

Pharmacophore-based virtual screening of catechol-o-methyltransferase (COMT) inhibitors to combat Alzheimer's disease.

Alzheimer's disease (AD) is one of the most significant neurodegenerative disorders and its symptoms mostly appear in aged people. Catechol-o-methyltransferase (COMT) is one of the known target enzymes responsible for AD. With the use of 23 known inhibitors of COMT, a query has been generated and validated by screening against the database of 1500 decoys to obtain the GH score and enrichment value. The crucial features of the known inhibitors were evaluated by the online ZINC Pharmer to identify new leads from a ZINC database. Five hundred hits were retrieved from ZINC Pharmer and by ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering by using FAF-Drug-3 and 36 molecules were considered for molecular docking. From the COMT inhibitors, opicapone, fenoldopam, and quercetin were selected, while ZINC63625100_413 ZINC39411941_412, ZINC63234426_254, ZINC63637968_451, and ZINC64019452_303 were chosen for the molecular dynamics simulation analysis having high binding affinity and structural recognition. This study identified the potential COMT inhibitors through pharmacophore-based inhibitor screening leading to a more complete understanding of molecular-level interactions.

Calix-Based Nanoparticles: A Review.

Calixarenes are considered as third generation supramolecules with hollow cavity-like architecture whereas nanoparticles are small entities with dimensions in the nanoscale. Many exciting achievements are seen when the calix system merges with nanoparticles which produces many fascinating facets in all fields of contemporary chemistry. The properties of nanoparticles which are tuned by calixarenes find applications in sensing, catalysis, molecular recognition, etc. Here, we have reviewed the chemistry of calix-based nanoparticles, and emphasis is laid on the modified, reducing, templated and stabilizing roles of calixarenes. This review covers the research being carried out in the domain of calix protected metal nanoparticles during last 18 years under the canopy of important 109 references. This article contains 58 figures which include 81 easy to understand structures. Calix-protected nanoparticles have enthralled researchers in the field of nanoscience with a tremendous growth in its applications, which heralds much promise to become in future a separate area of research.