Applications of Pyrrole and Pyridine-based Heterocycles in Cancer Diagnosis and Treatment.

BACKGROUND: The escalation of cancer worldwide is one of the major causes of economy burden and loss of human resources. According to the American Cancer Society, there will be 1,958,310 new cancer cases and 609,820 projected cancer deaths in 2023 in the United States. It is projected that by 2040, the burden of global cancer is expected to rise to 29.5 million per year, causing a death toll of 16.4 million. The hemostasis regulation by cellular protein synthesis and their targeted degradation is required for normal cell growth. The imbalance in hemostasis causes unbridled growth in cells and results in cancer. The DNA of cells needs to be targeted by chemotherapeutic agents for cancer treatment, but at the same time, their efficacy and toxicity also need to be considered for successful treatment. OBJECTIVE: The objective of this study is to review the published work on pyrrole and pyridine, which have been prominent in the diagnosis and possess anticancer activity, to obtain some novel lead molecules of improved cancer therapeutic. METHODS: A literature search was carried out using different search engines, like Sci-finder, Elsevier, ScienceDirect, RSC etc., for small molecules based on pyrrole and pyridine helpful in diagnosis and inducing apoptosis in cancer cells. The research findings on the application of these compounds from 2018-2023 were reviewed on a variety of cell lines, such as breast cancer, liver cancer, epithelial cancer, etc. Results: In this review, the published small molecules, pyrrole and pyridine and their derivatives, which have roles in the diagnosis and treatment of cancers, were discussed to provide some insight into the structural features responsible for diagnosis and treatment. The analogues with the chromeno-furo-pyridine skeleton showed the highest anticancer activity against breast cancer. The compound 5-amino-N-(1-(pyridin-4- yl)ethylidene)-1H-pyrazole-4-carbohydrazides was highly potent against HEPG2 cancer cell. Redaporfin is used for the treatment of cholangiocarcinoma, biliary tract cancer, cisplatin-resistant head and neck squamous cell carcinoma, and pigmentation melanoma, and it is in clinical trials for phase II. These structural features present a high potential for designing novel anticancer agents for diagnosis and drug development. CONCLUSION: Therefore, the N- and C-substituted pyrrole and pyridine-based novel privileged small Nheterocyclic scaffolds are potential molecules used in the diagnosis and treatment of cancer. This review discusses the reports on the synthesis of such molecules during 2018-2023. The review mainly discusses various diagnostic techniques for cancer, which employ pyrrole and pyridine heterocyclic scaffolds. Furthermore, the anticancer activity of N- and C-substituted pyrrole and pyridine-based scaffolds has been described, which works against different cancer cell lines, such as MCF-7, A549, A2780, HepG2, MDA-MB-231, K562, HT- 29, Caco-2 cells, Hela, Huh-7, WSU-DLCL2, HCT-116, HBL-100, H23, HCC827, SKOV3, etc. This review will help the researchers to obtain a critical insight into the structural aspects of pyrrole and pyridine-based scaffolds useful in cancer diagnosis as well as treatment and design pathways to develop novel drugs in the future.

Role of angiotensin pathway and its target therapy to rescue from experimental cerebral malaria.

Cerebral malaria (CM) induced by Plasmodium falciparum is a devastating neurological complication that may lead the patient to coma and death. This study aimed to protect Plasmodium-infected C57BL6 mice from CM by targeting the angiotensin II type 1 (AT1) receptor, which is considered the common connecting link between hypertension and CM. In CM, AT-1 mediates blood-brain barrier (BBB) damage through the overexpression of ß-catenin. The AT-1-inhibiting drugs, such as irbesartan and losartan, were evaluated for the prevention of CM. The effectiveness of these drugs was determined by the down regulation of ß-catenin, TCF, LEF, ICAM-1, and VCAM-1 in the drug-treated groups. The expression levels of VE-cadherin and vinculin, essential for the maintenance of BBB integrity, were found to be restored in the drug-treated groups. The pro-inflammatory cytokine levels were decreased, and the anti-inflammatory cytokine levels increased with the treatment. As a major highlight, the mean survival time of treated mice was found to be increased even in the absence of treatment with an anti-malarial agent. The combination of irbesartan or losartan with the anti-malarial agent α/ß-arteether has contributed to an 80% cure rate, which is higher than the 60% cure rate observed with α/ß-arteether alone treatment.

Metacaspase (Pf MCA-1) as antimalarial drug target: An in silico approach and their biological validation.

AIMS: Acquired drug resistance of Plasmodium is a global issue for the treatment of malaria. There are various proteases in the genome of Plasmodium falciparum (P. falciparum) including metacaspase-1 (PfMCA-1) that are essential and are being considered as an attractive drug target. It is aimed to identify novel therapeutics against malaria and their action on PfMCA-1 along with other apoptotic pathway events. MAIN METHODS: High throughput virtual screening of 55,000 compounds derived from Maybridge library was performed against PfMCA-1. Based on the docking score, sixteen compounds were selected for in vitro antimalarial screening against drug sensitive and resistant strains of P. falciparum using SYBR green-based assay. Subsequently, three lead molecules were selected and subjected to the evaluation of cytotoxicity, caspase like protease activity, mitochondrial membrane potential, ROS generation and DNA fragmentation via TUNEL assay. KEY FINDINGS: The in silico and in vitro approaches have brought forward some Maybridge library compounds with antiplasmodial activity most likely by enhancing the metacaspase activity. The compound CD11095 has shown better antimalarial efficacy, and KM06591 depicted higher caspase mediated killing, elevated TUNEL positive cells and moderate ROS generation. Mitochondrial membrane depolarization was augmented by RJC0069. Exposure of P. falciparum to CD11095, KM06591 and RJC0069 has ended up in parasite growth arrest via multiple mechanisms. SIGNIFICANCE: It is proposed that the Maybridge molecules CD11095, KM06591 and RJC0069 have antimalarial activity. Their mechanism of action was found to be by enhancing the metacaspases-like protease activity, mitochondrial depolarization and DNA fragmentation which stipulates significant insights towards promising candidates for drug development.

Reinvestigation of SnCl4 catalyzed efficient synthesis of 2,3-unsaturated glycopyranosides.

The Ferrier rearrangement is a powerful tool to prepare 2,3-unsaturated glycopyranosides. We have reinvestigated SnCl4 catalyzed Ferrier rearrangements through direct allylic substitution of the hydroxyl group at the C-3 position of glycals, resulting in the formation of stereoselective 2,3-unsaturated glycosides at 0 °C. The catalytic amount of SnCl4 (0.1 equiv.) was successfully used to promote this transformation on 3,4,6-tri-O-acetyl-D-glucal, 3,4,6-tri-O-acetyl-D-galactal and 3,4-di-O-acetyl-D-arabinal using various nucleophiles viz alcohols, azide and thiols to form a variety of 2,3-unsaturated glycopyranosides (pseudoglycals). This straightforward process is notable for its strong anomeric selectivity, excellent yields and shorter reaction time.

Fungal pectinases: an insight into production, innovations and applications.

The fungal system holds morphological plasticity and metabolic versatility which makes it unique. Fungal habitat ranges from the Arctic region to the fertile mainland, including tropical rainforests, and temperate deserts. They possess a wide range of lifestyles behaving as saprophytic, parasitic, opportunistic, and obligate symbionts. These eukaryotic microbes can survive any living condition and adapt to behave as extremophiles, mesophiles, thermophiles, or even psychrophile organisms. This behaviour has been exploited to yield microbial enzymes which can survive in extreme environments. The cost-effective production, stable catalytic behaviour and ease of genetic manipulation make them prominent sources of several industrially important enzymes. Pectinases are a class of pectin-degrading enzymes that show different mechanisms and substrate specificities to release end products. The pectinase family of enzymes is produced by microbial sources such as bacteria, fungi, actinomycetes, plants, and animals. Fungal pectinases having high specificity for natural sources and higher stabilities and catalytic activities make them promising green catalysts for industrial applications. Pectinases from different microbial sources have been investigated for their industrial applications. However, their relevance in the food and textile industries is remarkable and has been extensively studied. The focus of this review is to provide comprehensive information on the current findings on fungal pectinases targeting diverse sources of fungal strains, their production by fermentation techniques, and a summary of purification strategies. Studies on pectinases regarding innovations comprising bioreactor-based production, immobilization of pectinases, in silico and expression studies, directed evolution, and omics-driven approaches specifically by fungal microbiota have been summarized.

Antileishmanial evaluation of triazole-butenolide conjugates: design, synthesis, in vitro screening, SAR and in silico ADME predictions.

In the quest to discover novel scaffolds with leishmanicidal effects, a series of 23 compounds containing the most promising 1,2,3-triazole and highly potent butenolide in one framework were synthesized. The synthesized conjugates were screened against Leishmania donovani parasite; five of them showed moderate antileishmanial activity against promastigotes (IC50 30.6 to 35.5 µM) and eight of them exhibited significant activity against amastigotes (IC50 ≤12 µM). Compound 10u was found to be the most active (IC50 8.4 ± 0.12 µM) with the highest safety index (20.47). The series was further evaluated against Plasmodium falciparum (3D7 strain) and seven compounds were found to be moderately active. Among them, again 10u emerged as the most active compound (IC50 3.65 µM). In antifilarial assays against adult female Brugia malayi, five compounds showed grade II inhibition (50-74%). Structure-activity relationship (SAR) analysis suggested a substituted phenyl ring, triazole and butenolide as essential structural features for bioactivity. Moreover, the results of in silico ADME parameter and pharmacokinetic studies indicated that the synthesized triazole-butenolide conjugates abide by the required criteria for the development of orally active drugs, and thus this scaffold can be used as a pharmacologically active framework that should be considered for the development of potential antileishmanial hits.

Design, synthesis and evaluation of novel pyrrole-hydroxybutenolide hybrids as promising antiplasmodial and anti-inflammatory agents.

In the pursuance of novel scaffolds with promising antiplasmodial and anti-inflammatory activity, a series of twenty-one compounds embraced with most promising penta-substituted pyrrole and biodynamic hydroxybutenolide in single skeleton was designed and synthesized. These pyrrole-hydroxybutenolide hybrids were evaluated against Plasmodium falciparum parasite. Four hybrids 5b, 5d, 5t and 5u exhibited good activity with IC50 of 0.60, 0.88, 0.97 and 0.96 µM for chloroquine sensitive (Pf3D7) strain and 3.92, 4.31, 4.21 and 1.67 µM for chloroquine resistant (PfK1) strain, respectively. In vivo efficacy of 5b, 5d, 5t and 5u was studied against the P. yoelii nigeriensis N67 (a chloroquine-resistant) parasite in Swiss mice at a dose of 100 mg/kg/day for 4 days via oral route. 5u was found to show maximum 100% parasite inhibition with considerably increased mean survival time. Simultaneously, the series of compounds was screened for anti-inflammatory potential. In preliminary assays, nine compounds showed more than 85% inhibition in hu-TNFα cytokine levels in LPS stimulated THP-1 monocytes and seven compounds showed more than 40% decrease in fold induction in reporter gene activity analyzed via Luciferase assay. 5p and 5t were found to be most promising amongst the series, thus were taken up for further in vivo studies. Wherein, mice pre-treated with them showed a dose dependent inhibition in carrageenan induced paw swelling. Moreover, the results of in vitro and in vivo pharmacokinetic parameters indicated that the synthesized pyrrole-hydroxybutenolide conjugates abide by the required criteria for the development of orally active drug and thus this scaffold can be used as pharmacologically active framework that should be considered for the development of potential antiplasmodial and anti-inflammatory agents.

Incorporation of Trifluoromethyltriazoline in the Side Chain of 4-Aminoquinolines: Synthesis and Evaluation as Antiplasmodial Agents.

Reported herein is the identification of a novel class of 4-aminoquinoline-trifluormethyltriazoline compounds as possible antiplasmodial agents. The compounds were accessed through a silver-catalyzed three-component reaction of trifluorodiazoethane with in situ generated Schiff base from corresponding quinolinylamine and aldehydes. While attempting to incorporate a sulfonyl moiety, the triazoline formed underwent spontaneous oxidative aromatization to afford triazole derivatives. All synthesized compounds were tested for their antimalarial potential in vitro and in vivo. Out of 32 compounds, four showed the most promising antimalarial activity with IC50 values ranging from 4 to 20 nM against Pf3D7 (chloroquine-sensitive) and from 120 to 450 nM against PfK1 (chloroquine-resistant) strains. One of these compounds was also found to be effective in animal studies; it showed a 99.9 % decrease in parasitic load on day 7 post-infection along with a 40 % cure rate and longest host life span.

Effect of carbon quantum dots derived from extracts of UV-B-exposed Eclipta alba on alcohol-induced liver cirrhosis in Golden Hamster.

The Eclipta alba plant is considered hepatoprotective, owing to its phytoconstituents wedelolactone. In the current study, effect of elevated ultraviolet-B (eUV-B) radiation was investigated on biochemical, phytochemical, and antioxidative enzymatic activities of E. alba (Bhringraj) plant. The UV-B exposure resulted in an increase in oxidative stress, which has caused an imbalance in phytochemical, biochemical constituents, and induced antioxidative enzymatic activities. It was observed that the UV-B exposure promoted wedelolactone yield by 23.64%. Further, the leaf extract of UV-B-exposed plants was used for the synthesis of carbon quantum dots (CQDs) using low cost, one-step hydrothermal technique and its biocompatibility was studied using in vitro MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay on HepG2 liver cell line. It revealed no toxicity in any treatment groups in comparison to the control. Both CQDs and leaf extract were orally administered to the golden hamster suffering from alcohol-induced liver cirrhosis. In the morphometric study, it was clearly observed that a combination of UV-B-exposed leaf extract and synthesized CQDs delivered the best result with maximum recovery of liver tissues. The present study reveals the positive impact of UV-B exposure on the medicinally important plant, increased yield of wedelolactone, and its enhanced hepatoprotective efficacy for the treatment of damaged liver tissues.

Exciton Manipulation for Enhancing Photoelectrochemical Hydrogen Evolution Reaction in Wrinkled 2D Heterostructures.

2D materials' junctions have demonstrated capabilities as metal-free alternatives for the hydrogen evolution reaction (HER). To date, the HER has been limited to heterojunctions of different compositions or band structures. Here, the potential of local strain modulation based on wrinkled 2D heterostructures is demonstrated, which helps to realize photoelectrocatalytically active junctions. By forming regions of high and low tensile strain in wrinkled WS2 monolayers, local modification of their band structure and internal electric field due to piezoelectricity is realized in the lateral direction. This structure produces efficient electron-hole pair generation due to light trapping and exciton funneling toward the crest of the WS2 wrinkles and enhances exciton separation. Additionally, the formation of wrinkles induces an air gap in-between the 2D layer and substrate, which reduces the interfacial scattering effect and consequently improves the charge-carrier mobility. A detailed study of the strain-dependence of the photocatalytic HER process demonstrates a 2-fold decrease in the Tafel slope and a 30-fold enhancement in exchange current density. Finally, optimization of the light absorption through functionalization with quantum dots produces unprecedented photoelectrocatalytic performance and provides a route toward the scalable formation of strain-modulated WS2 nanojunctions for future green energy generation.

Molecular and immunological characterization of the calcyclin binding protein in rodent malaria parasite.

Malaria remains as a global life-threatening disorder due to the emergence of resistance against standard antimalarials. Consequently, there is a serious need to better understand the biology of the malaria parasite in order to determine appropriate targets for new interventions. Calcyclin binding protein (CacyBP) is a multi-functional and multi-ligand protein that is not well characterized in malaria disease. In this study, we have cloned CacyBP from rodent species Plasmodium yoelii nigeriensis and purified the recombinant protein to carry out its detailed molecular, biophysical and immunological characterization. Molecular characterization indicates that PyCacyBP is a ∼27 kDa protein in parasite lysate and exists in monomer and dimer forms. Bioinformatic analysis of CacyBP showed significant sequence and structural similarities between rodent and human malaria parasites. CacyBP is expressed in all blood stages of P. yoelii nigeriensis parasite. In silico studies proposed the immunogenic potential of CacyBP. The rPyCacyBP immunized mice exhibited elevated levels of IgG1, IgG2a, IgG2b and IgG3 in their serum. Notably, cellular immune response in splenocytes from immunized mice showed increased expression of pro-inflammatory cytokines such as IL-12, IFN-γ and TNF-α. This CacyBP exhibited pro-inflammatory immune response in rodent host. These finding revealed that CacyBP may have the potential to boost the host immunity for protection against malaria infection. The present study provides basis for further exploration of the biological function of CacyBP in malaria parasite.

Genome mining of Fusarium reveals structural and functional diversity of pectin lyases: a bioinformatics approach.

Pectin lyase (PNL) is an important enzyme of the pectinases group which degrades pectin polymer to 4,5-unsaturated oligogalacturonides by a unique ß-elimination mechanism and is used in several industries. The existence of multigene families of pectin lyases has been investigated by mining microbial genomes. In the present study, 52 pectin lyase genes were predicted from sequenced six species of Fusarium, namely F. fujikuroi, F. graminearum, F. proliferatum, F. oxysporum, F. verticillioides and F. virguliforme. These sequences were in silico characterized for several physico-chemical, structural and functional attributes. The translated PNL proteins showed variability with 344-1142 amino acid residues, 35.44-127.41 kDa molecular weight, and pI ranging from 4.63 to 9.28. The aliphatic index ranged from 75.33 to 84.75. Multiple sequence alignment analysis showed several conserved amino acid residues and five distinct groups marked as I, II, III, IV, and V were observed in the phylogenetic tree. The Three-dimensional Structure of five of these PNLs, each representing a distinct group of phylogenetic trees was predicted using I-TASSER Server and validated. The pectin lyase proteins of Fusarium species revealed close similarity with pectin lyase of Aspergillus niger PelA(1IDJ) and PelB(1QCX). Diversity in the structural motifs was observed among Fusarium species with 2 ß-sheets, 1 ß-hairpin, 7-12 ß bulges, 18-25 strands, 6 -11 helices, 1 helix-helix interaction, 32-49 ß turns, 2-6 γ turns and 2- 3 disulfide bonds. The unique Pec_lyase domain was uniformly observed among all PNL proteins confirming its identity. The genome-wide mining of Fusarium species was attempted to provide the diversity of PNL genes, which could be explored for diverse applications after performing cloning and expression studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03333-w.

Synthesis and Antimalarial Activity of 4-Methylaminoquinoline Compounds against Drug-Resistant Parasite.

A series of novel 4-aminoquinoline analogues bearing a methyl group at 4-aminoquinoline moiety were synthesized via a new and robust synthetic route comprising in situ tert-butoxycarbonyl (Boc) deprotection-methylation cascade resulting in the corresponding N-methylated secondary amine using Red-Al and an efficient microwave-assisted strategy for the fusion of N-methylated secondary amine with 4-chloroquinoline nucleus to access the series of novel 4-N-methylaminoquinoline analogues. The new series of compounds were evaluated for their antimalarial activity in in vitro and in vivo models. Among 21 tested compounds, 9a-i have shown a half-maximal inhibitory concentration (IC50) value less than 0.5 µM (i.e., <500 nM) against both chloroquine-sensitive strain 3D7 and chloroquine-resistant strain K1 of Plasmodium falciparum with acceptable cytotoxicity. Based on the in vitro antimalarial activity, selected compounds were screened for their in vivo antimalarial activity against Plasmodium yoelii nigeriensis (a multidrug-resistant) parasite in Swiss mice. Most of the compounds have shown significant inhibition on day 4 post infection at the oral dose of 100 mg/kg. Compound 9a has shown 100% parasite inhibition on day 4, and out of five treated mice, two were cured till the end of the experiment. The present study suggests that 4-methylamino substitution is well tolerated for the antiplasmodial activity with reduced toxicity and therefore will be highly useful for the discovery of a new antimalarial agent against drug-resistant malaria.

Large Area Few-Layer Hexagonal Boron Nitride as a Raman Enhancement Material.

Increasingly, two-dimensional (2D) materials are being investigated for their potential use as surface-enhanced Raman spectroscopy (SERS) active substrates. Hexagonal Boron Nitride (hBN), a layered 2D material analogous to graphene, is mostly used as a passivation layer/dielectric substrate for nanoelectronics application. We have investigated the SERS activity of few-layer hBN film synthesized on copper foil using atmospheric pressure chemical vapor deposition. We have drop casted the probe molecules onto the hBN substrate and measured the enhancement effect due to the substrate using a 532 nm excitation laser. We observed an enhancement of ≈103 for malachite green and ≈104 for methylene blue and rhodamine 6G dyes, respectively. The observed enhancement factors are consistent with the theoretically calculated interaction energies of MB > R6G > MG with a single layer of hBN. We also observed that the enhancement is independent of the film thickness and surface morphology. We demonstrate that the hBN films are highly stable, and even for older hBN films prepared 7 months earlier, we were able to achieve similar enhancements when compared to freshly prepared films. Our detailed results and analyses demonstrate the versatility and durability of hBN films for SERS applications.

Repurposing of existing therapeutics to combat drug-resistant malaria.

In the era of drug repurposing, speedy discovery of new therapeutic options for the drug-resistant malaria is the best available tactic to reduce the financial load and time in the drug discovery process. Six anticancer drugs, three immunomodulators and four antibiotics were selected for the repositioning against experimental malaria owing to their mode of action and published literature. The efficacy of existing therapeutics was evaluated against chloroquine-resistant in vitro and in vivo strains of Plasmodium falciparum and P. yoelii, respectively. All the pre-existing FDA-approved drugs along with leptin were primarily screened against chloroquine-resistant (PfK1) and drug-sensitive (Pf3D7) strains of P. falciparum using SYBR green-based antiplasmodial assay. Cytotoxic profiling of these therapeutics was achieved on Vero and HepG2 cell lines, and human erythrocytes. Percent blood parasitemia and host survival was determined in chloroquine-resistant P. yoelii N67-infected Swiss mice using appropriate doses of these drugs/immunomodulators. Antimalarial screening together with cytotoxicity data revealed that anticancer drugs, idelalisib and 5-fluorouracil acquired superiority over their counterparts, regorafenib, and tamoxifen, respectively. ROS-inducer anticancer drugs, epirubicin and bleomycin were found toxic for the host. Immunomodulators (imiquimod, lenalidomide and leptin) were safest but less active in in vitro system, however, in P. yoelii-infected mice, they exhibited modest parasite suppression at their respective doses. Among antibiotics, moxifloxacin exhibited better antimalarial prospective than levofloxacin, roxithromycin and erythromycin. 5-Fluorouracil, imiquimod and moxifloxacin displayed 97.64, 81.18 and 91.77 % parasite inhibition in treated animals and attained superiority in their respective groups thus could be exploited further in combination with suitable antimalarials.

Synthesis and characterization of novel protein nanodots as drug delivery carriers with an enhanced biological efficacy of melatonin in breast cancer cells.

Melatonin is a potent antioxidant, chemotherapeutic and chemo preventive agent against breast cancer. However, its short half-life is one of the major limitations in its application as a therapeutic drug. To overcome this issue, the green-emitting protein nanodot (PND) was synthesized by a one-step hydrothermal method for loading melatonin. The synthesized pH-7 and pH-2 PND showed a quantum yield of 22.1% and 14.0%, respectively. The physicochemical characterization of both PNDs showed similar morphological and functional activities. Furthermore, the biological efficacy of melatonin-loaded PND (MPND) was evaluated in a breast cancer cell line (MDA-MB-231) for live-cell imaging and enhanced nano-drug delivery efficacy. Interestingly, the permeability of neutral pH PND in both cell cytoplasm and nucleus nullifies the limitations of real-time live-cell imaging, and ensures nuclear drug delivery efficacy. Neutral pH PND showed better cell viability and cytotoxicity as a fluorescence bioimaging probe compared to acidic PND. The bioavailability and cell cytotoxicity effect of MPND on MDA-MB-231 breast cancer cells were studied through confocal and migration assay. Results showed that MPND causes enhanced bioavailability, better cellular uptake, and inhibition of the migration of breast cancer cells as compared to the drug alone. Besides, the synthesized MPND showed no sign of fluorescence quenching even at a high concentration of melatonin, making it an ideal nanocarrier for bioimaging and drug delivery.

An updated and comprehensive review of the antiviral potential of essential oils and their chemical constituents with special focus on their mechanism of action against various influenza and coronaviruses.

Essential oils and their chemical constituents have been reported with well documented antimicrobial effects against a range of bacterial, fungal and viral pathogens. By definition, essential oils are a complex mixture of volatile organic compounds which are synthesized naturally in different parts of the plant as part of plants secondary metabolism. The chemical composition of the essential oils is dominated by the presence of a range of compounds including phenolics, terpenoids, aldehydes, ketones, ethers, epoxides and many others inferring that essential oils must be effective against a wide range of pathogens. This review article mainly focuses on the antiviral potential of essential oils and their chemical constituents especially against influenza and coronaviruses. Essential oils have been screened against several pathogenic viruses, including influenza and other respiratory viral infections. The essential oils of cinnamon, bergamot, lemongrass, thyme, lavender have been reported to exert potent antiviral effects against influenza type A virus. The essential oil of Citrus reshni leaves has been shown to be effective against H5N1 virus. The essential oil of Lippia species at a concentration of 11.1 µg/mL has been shown to induce 100% inhibition of yellow fever virus in Vero cells. Essential oils and oleoresins have been shown through in vitro and in vivo experiments to induce antiviral effects against Coronavirus infectious bronchitis virus. A study reported 221 phytochemical compounds and essential oils to be effective against severe acute respiratory syndrome associated coronavirus (SARS-CoV) using a cell-based assay measuring SARS-CoV-induced cytopathogenic effect on Vero E6 cells. The main mechanism of antiviral effects of essential oils has been found to cause capsid disintegration and viral expansion which prevents the virus to infect host cells by adsorption via the capsid. Essential oils also inhibit hemagglutinin (an important membrane protein of various viruses) of certain viruses; this membrane protein allows the virus to enter the host cell. Many essential oils and their components could inhibit the late stages of viral life cycle by targeting the redox signalling pathway. Essential oils of Thymus vulgaris, cymbopogon citratus and Rosmarinus officinalis have been found to destabilize the Tat/TAR-RNA complex of HIV-1 virus, this complex being essential for HIV-1 replication. Being lipophilic in nature, essential oils can penetrate viral membranes easily leading to membrane disintegration. The current comprehensive review will facilitate researchers to find chemical entities from plant sources as possible inhibitory agents against various viruses.

Printability assessment of psyllium husk (isabgol)/gelatin blends using rheological and mechanical properties.

The primary goal of this study is to highlight the rheological and mechanical properties of a new blend composed of naturally-derived hydrogel materials- psyllium husk (PH) and gelatin (G) for its potential use in three-dimensional (3D) printing technology. The mixtures were prepared at various weight ratios of 100PH, 75PH + 25G and 50PH + 50G. A suitable selection of the printable ink was made based on the preliminary screening steps of manual filament drop test and layer stacking by 3D printing. Printing of the common features such as hexagon and square grids helped evaluating shape fidelity of the chosen ink. Although 50PH + 50G blend was found meeting most of the criteria for an ideal 3D printable ink, rheological and mechanical characterizations have been performed for all the ratios of polymeric blends. This study documents the correlation between various factors of rheology that should be taken into account while categorizing any biomaterial as a printable ink. Yield stress was measured as 18.59 ± 4.21 Pa, 268.74 ± 13.56 Pa and 109.16 ± 9.85 Pa for 50PH + 50G, 75PH + 25G and 100PH, respectively. Similarly, consistency index (K) and flow index (n) were calculated using the power law equation and found as 49.303 ± 4.17, 530.59 ± 10.92, 291.82 ± 10.53 and 0.275 ± 0.04, 0.05 ± 0.005, 0.284 ± 0.04 for 50PH + 50G, 75PH + 25G and 100PH, respectively. The loss modulus (G″) was observed dominating over storage modulus (G') for 50PH + 50G, that depicts its liquid-like property; whereas storage modulus (G') was found dominating in case of 75PH + 25G and 100PH, indicating their solid-like characteristics. In addition, the loss tangent value (tan δ) of 50PH + 50G was observed exceeding unity (1.05), supporting its plastic behavior, unlike 75PH + 25G (0.5) and 100PH (0.33) whose loss tangent values were estimated less than unity revealing their elastic behavior. Also, 50PH + 50G was found to have the highest mechanical strength amongst the three blends with a Young's modulus of 9.170 ± 0.0881 kPa.

Self-Sufficient and Highly Efficient Gold Sandwich Upconversion Nanocomposite Lasers for Stretchable and Bio-applications.

Multifunctional lanthanide-doped upconversion nanoparticles (UCNPs) have spread their wings in the fields of flexible optoelectronics and biomedical applications. One of the ongoing challenges lies in achieving UCNP-based nanocomposites, which enable a continuous-wave (CW) laser action at ultralow thresholds. Here, gold sandwich UCNP nanocomposites [gold (Au1)-UCNP-gold (Au2)] capable of exhibiting lasing at ultralow thresholds under CW excitation are demonstrated. The metastable energy-level characteristics of lanthanides are advantageous for creating population inversion. In particular, localized surface plasmon resonance-based electromagnetic hotspots in the nanocomposites and the huge enhancement of scattering coefficient for the formation of coherent closed loops due to multiple scattering facilitate the process of stimulated emissions as confirmed by theoretical simulations. The nanocomposites are subjected to stretchable systems for enhancing the lasing action (threshold ∼ 0.06 kW cm-2) via a light-trapping effect. The applications in bioimaging of HeLa cells and antibacterial activity (photothermal therapy) are demonstrated using the newly designed Au1-UCNP-Au2 nanocomposites.

DNA biodots based targeted theranostic nanomedicine for the imaging and treatment of non-small cell lung cancer.

The light absorption and emission characteristics of DNA biodots (DNA-BD), along with biocompatibility, give them a high potential for use in various medical applications, particularly in diagnostic purpose. DNA, under high pressure and temperature, condenses to form luminescent biodots. The objective of this research is to develop DNA-biodots (BD) loaded and cetuximab conjugated targeted theranostic liposomes of etoposide for lung cancer imaging and therapy. Theranostic liposomes were prepared by using the solvent injection method and characterized for their particle size, polydispersity, zeta potential, encapsulation efficiency, and pH-dependent in-vitro release, SEM, TEM AFM, EDX, and XRD. The t50% (time at which 50% of the drug releases from the preparation) of the formulations was pH-dependent, with a significant increase in the release at lower pH (5.5). To kill A549 adenocarcinoma cells, the etoposide (control) required significantly (p < 0.05) higher drug concentrations in comparison to non-targeted and; the non-targeted formulation required more concentrations in comparison to targeted liposomes. The in-vivo results demonstrated that CTX-TPGS decorated theranostic liposomes could be a promising carrier for lung theranostics due to their nano-size and selectivity towards EGFR overexpressed cells which provided an improved NSCLC targeted delivery of ETP in comparison to the non-targeted and control formulations.