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1,3,4-Oxadiazole-based heterocyclic analogs (3a–3m) were synthesized via cyclization of Schiff bases with substituted aldehydes in the presence of bromine and acetic acid. The structural clarification of synthesized molecules was carried out with various spectroscopic techniques such as FT-IR, 1H and 13C-NMR, UV–visible spectroscopy, mass spectrometry (LCMS). The TD-DFT studies were also confirmed the structure of drug molecules. In vitro antifungal activity was performed against C. Albicans, C. glabrata and C. tropicalis and analogs 3g, 3i, and 3m showed potent MIC at 200 µg/ml and excellent ZOI measurements of 17-21 nm. The cell viability on human hepatoma cells (Huh7) for lead molecules 3g, 3i, and 3m was found to be 99.5%, 92.3%, and 86.9% at 20 μM, 10 μM, and 20 μM respectively. The antioxidant activity of the lead molecules 3g, 3i, and 3m were estimated and exhibited great IC50 values of 0.104 ± 0.021, 0.145 ± 0.05, and 0.165 ± 0.018 μg/mL with DPPH and 0.107 ± 0.04, 0.191 ± 0.12, and 0.106 ± 0.08 with H2O2 respectively. The DNA binding interaction mode for the lead molecules was also carried out with Ct-DNA using the absorption, emission, CV, CD, and Time resolve fluorescence techniques. The results showed good binding constant (Kb) values 9.1×105, 9.94×105, and 9.32×105 M−1 for 3g, 3i, and 3m respectively. The results were further validated by In-silico molecular docking and pharmacokinetics properties of lead drug molecules were also studied with PDB ID: 1BNA and 5FSA to explore the best hits.

Malaria still threatens half the globe population despite successful Artemisinin-based combination therapy. One of the reasons for our inability to eradicate malaria is the emergence of resistance to current antimalarials. Thus, there is a need to develop new antimalarials targeting Plasmodium proteins. The present study reported the design and synthesis of 4, 6 and 7-substituted quinoline-3-carboxylates 9(a–o) and carboxylic acids 10(a–b) for the inhibition of Plasmodium N-Myristoyltransferases (NMTs) using computational biology tools followed by chemical synthesis and functional analysis. The designed compounds exhibited a glide score of −9.241 to −6.960 kcal/mol for PvNMT and −7.538 kcal/mol for PfNMT model proteins. Development of the synthesized compounds was established via NMR, HRMS and single crystal X-ray diffraction study. The synthesized compounds were evaluated for their in vitro antimalarial efficacy against CQ-sensitive Pf3D7 and CQ-resistant PfINDO lines followed by cell toxicity evaluation. In silico results highlighted the compound ethyl 6-methyl-4-(naphthalen-2-yloxy)quinoline-3-carboxylate (9a) as a promising inhibitor with a glide score of −9.084 kcal/mol for PvNMT and −6.975 kcal/mol for PfNMT with IC50 values of 6.58 µM for Pf3D7 line. Furthermore, compounds 9n and 9o exhibited excellent anti-plasmodial activity (Pf3D7 IC50 = 3.96, 6.71 µM, and PfINDO IC50 = 6.38, 2.8 µM, respectively). The conformational stability of 9a with the active site of the target protein was analyzed through MD simulation and was found concordance with in vitro results. Thus, our study provides scaffolds for the development of potent antimalarials targeting both Plasmodium vivax and Plasmodium falciparum. Communicated by Ramaswamy H. Sarma

In order to develop a potent antifungal agent, a carbothioamide-based pyrazoline derivative (3a) was synthesized. Molecular structure of compound has been confirmed using spectroscopic techniques viz. FT-IR, UV-visible, NMR, Raman spectroscopy, mass spectrometry and single crystal X-ray crystallography. Furthermore, potential antifungal activity of compound 3a was screened against three candida strains such as C. albicans, C. glabrata and C. tropicalis. For antifungal experimental validated by molecular docking study with sterol 14a-demethylase (CYP51) (PDB ID: 5JLC, 5V5Z, 6T1U) by using the Autodock Vina software. Antioxidant assay results suggested that compound possesses good radical scavenging activity against diverse free radical (DPPH). The intercalative mode of interaction of compound with Calf thymus DNA (Ct-DNA) was confirmed from spectroscopic techniques such as UV-vis., fluorescence, cyclic voltammetry and competitive assay using ethidium bromide. B3LYP technique and 6-311 ++ G (d, p) basis set were employed to optimize molecular structure and calculate wavenumbers of normal vibrational modes. A complete depiction of the intermolecular interactions on crystal surfaces is provided by Hirshfeld surface analysis, and fingerprint plots were found. The computed parameters and the experimental bond lengths and bond angles were in good agreement. The chemical shifts of the 1H and 13C-NMR spectra were estimated using the GIAO method and experimental spectra were contrasted. With the aid of the TD-DFT approach and the PCM solvent model, electronic characteristics like UV-Vis (in gas phase, ethanol and DMSO) were examined. The outcomes were then compared to experimental UV-Vis spectra.

An oxadiazole derivative 2 was prepared by condensation reaction through cyclization of semicarbazone in the presence of bromine; the structural confirmation was supported by

β-citronellol, an acyclic monoterpenoid, inhibits dose-dependent growth of C. glabrata and C. tropicalis with MIC/MFC values of 400 µg/ml/600 µg/ml and 100 µg/ml/200 µg/ml, respectively. Below MIC,...

COVID-19 pandemic has shown greater severity in people with co-morbidities; diabetes being the leading cause of higher mortality rates in COVID-19 patients. Besides compromised immunity, there are other factors that make diabetics more prone to SARS-CoV-2 infection. To date, there is no clinically proven treatment for this disease, but fortunately there are several reports of vaccines in different stages of development. This review compiles some commonly used anti-diabetic drugs and their probable efficacy during a COVID-19 attack. This is also an attempt to understand the cause of severity of SARS-CoV-2 infection in diabetic patients. Until a proper cure or approved vaccine is available, it is best to manage the disease by improving the immune status and making use of already available drugs that show potential against the virus.

The use of aqueous cyanobacterial extracts for selenium nanoparticle (SeNP) synthesis is considered green, cost-effective, and eco-friendly technology that is more advanced than physical and chemical methods. In the current study, an aqueous extract of Arthrospira indica SOSA-4 was used as a reducing and stabilizing agent for the green synthesis of SeNPs. The UV-Visible absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-Ray diffraction, Raman spectroscopy, Atomic force microscopy (AFM), Scanning electron microscopy-Energy Dispersive X-Ray spectroscopy(SEM-EDX), and Transmission electron microscopy (TEM) were performed to characterize the biosynthesized SeNPs. Gas chromatography-Mass spectrometry (GC-MS) was also performed to know the composition of the cyanobacterial extract. SEM, TEM, and AFM showed the average size of SeNPs to be 8.5 nm, 9 nm, and 8.7 nm respectively. FT-IR analysis demonstrated the presence of functional groups on the SeNPs that acted as stabilizing agents. XRD pattern and Raman spectroscopy showed the amorphous nature of SeNPs. Synthesized SeNPs showed significant antioxidant activity in DPPH, FRAP, SOR, and ABTS assay. SeNPs showed good anti-microbial activity against Staphylococcus aureus, Escherichia coli, Candida albicans, Candida glabrata, and Candida tropicalis and good anti-cancer activity in MTT assay, Trypan assay, and Flow cytometry analysis against MCF-7, SiHa, and SW480 cell lines. Non-toxicity of SeNPs against normal cell line (HEK-293) was an additional property that affirmed its potential as a bio-compatible nanomaterial.

The problem of antibiotic resistance has prompted researchers around the globe to search for new antimicrobial agents. Antimicrobial proteins and peptides are naturally secreted by almost all the living organisms to fight infections and can be safer alternatives to chemical antibiotics. Lactoferrin (LF) is a known antimicrobial protein present in all body secretions. In this study, LF was digested by trypsin, and the resulting hydrolysates were studied with respect to their antimicrobial properties. Among the hydrolysates, a 21-kDa basic fragment of LF (termed lactosmart) showed promise as a new potent antimicrobial agent. The antimicrobial studies were performed on various microorganisms including Shigella flexneri, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli as well as fungal pathogens such as Candida albicans, Candida tropicalis, and Candida glabrata. In addition, the lipopolysaccharide (LPS)-binding properties of lactosmart were studied using surface plasmon resonance technique in vitro, along with docking of LPS and molecular dynamics (MD) simulation studies. The results showed that lactosmart had better inhibitory effects against pathogenic microorganisms compared to LF. The results of docking and MD simulation studies further validated the tighter binding of LPS to lactosmart compared to LF. The two LPS-binding sites have been characterized structurally in detail. Through these studies, it has been demonstrated that in native LF, only one LPS-binding site remains exposed due to its location being on the surface of the molecule. However, due to the generation of the lactosmart molecule, the second LPS-binding site gets exposed too. Since LPS is an essential and conserved part of the bacterial cell wall, the pro-inflammatory response in the human body caused by LPS can be targeted using the newly identified lactosmart. These findings highlight the immense potential of lactosmart in comparison to native LF in antimicrobial defense. We propose that lactosmart can be further developed as an antibacterial, antifungal, and antibiofilm agent.

A series of heterocyclic analogs (2a-2l) was synthesized through condensation of 5-(4-aminophenyl)-1,3,4-oxadiazole-2-thiol and substituted aldehydes in ethanol and characterized by 1H, 13C NMR, IR, UV–visible spectroscopy and mass spectrometry. Optimization of the structure of heterocyclic analogs 2c, 2h and 2j was done by density functional theory (DFT) calculations. In vitro antifungal activity and growth pattern analyses of heterocyclic analogs (2a-2l) were evaluated against the Candida albicans. Results exhibited that analog 2c has significant antifungal potential with MIC value of 200 µg/ml comparable with standard drug fluconazole. In vitro hemolysis assay of the analog 2c showed 7.27% hemolysis at 200 µg/ml concentration indicating its nontoxic nature. The interaction of promising compound 2c with CT-DNA was carried out by UV-visible, fluorescence, Time-Resolved fluorescence spectrophotometry, cyclic voltammetry, circular dichroism and viscosity measurements. The UV-visible spectral analysis signifies the formation of complex between heterocyclic analog 2c and CT-DNA. The binding constant (Kb) and Gibb's free energy (ΔG) for 2c were found to be 6.34 × 105 and -33.1 KJmol−1, respectively. Further from fluorescence spectra, linear Stern–Volmer constant (KSV) for 2c was found to be 1.29 × 105. In silico molecular docking study of analog 2c with PDB: 1BNA confirmed the intercalation mode of binding which were corroborated with in vitro DNA binding results. The interaction study of analog 2c with supercoiled pBR322 plasmid DNA with varying concentration (3–20 mM) was carried out by Agarose gel electrophoresis. Antioxidant activity was also carried out for compounds 2a-2l using DPPH and H2O2 assay.