Gallic Acid Derived 1, 2-Diarylindole as a Potential Antifungal Agent against Candida Strain.

BACKGROUND: In recent decades, Candida albicans has become a serious issue for public health. The worldwide rapid rise in drug resistance to conventional therapies is the main contributing reason. Moreover, because of their potent activity at low concentrations and apparent lack of toxicity, compounds originating from plants are used in therapeutic treatments because of their potent activity at low concentrations and apparent lack of toxicity. Particularly in immunocompromised people, Candida species can result in a wide range of ailments. OBJECTIVES: Present manuscript describes antifungal activity of an indole derivative 1-(4-((5- methoxy-2-(3,4,5-trimethoxyphenyl)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1- amine (7, 100DL-6) by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS- Delhi). METHODS: The synthetic strategy for the preparation of indole derivatives was modified through Fischer indole reaction. Antifungal activity of an indole derivative 1-(4-((5-methoxy-2-(3,4,5- trimethoxyphenyl)-1H-indol-1-yl) methyl) phenoxy)-N,N-dimethylethan-1-amine (7, 100DL-6) was done by using an in-silico and in-vitro anti-candidal activity against two Candida strains; Candida kefyr-DS-02 (ATCC-204093) and Candida albicans (AI-clinical isolate, AIIMS-Delhi). Compound 100DL-6 efficacy was determined by Combination synergy study, ergosterol binding assay, MTT toxicity study and Mutagenicity. RESULTS: Compound 100DL-6 was obtained in 65% yield on desired motifs. Docking scores found were 100DL-6 (-8.7 kcal/mol) and Fluconazole (-7.6 kcal/mol). Further, RMSD were shown for 100DL6 (0.26 ± 0.23 nm) and fluconazole (1.2 ± 0.62 nm). Indole derivative 100DL-6 was active against the tested fungal pathogens and the total zone of inhibition was measured between 13-14 mm in diameter and MIC values between 31.25 µg/mL to 250 µg/mL and MFC values between 62.5 µg/mL to 500 µg/mL. In checkerboard assay synergistic mode of interaction of 100DL-6 with known antifungal drugs was observed. In the presence of ergosterol 100DL-6 and standard drug (s) increased their MIC values, demonstrating a considerable affinity for ergosterol. Compound 100DL-6 was considered to be less-cytotoxic to the cells as determined by MTT assay. Lead compound 100DL-6 was found to be non-mutagenic. CONCLUSION: In the present study, 100DL6 (indole derivatives) significantly abrupted the ergosterol biosynthetic pathway and showed moderate anti-candidal effects. These studies suggest that 100DL6 significantly enhances antifungal effect of clinical drug fluconazole synergistically and may be considered as in clinical trial prior to some extensive in-vivo validations.

Synergistic Antibacterial Activity of Gallic Acid Based Chalcone Indl 2 by Inhibiting Efflux Pump Transporters.

As a part of novel discovery of drugs from natural resources, present study was undertaken to explore the antibacterial potential of chalcone Indl-2 in combination with different group of antibiotics. MIC of antibiotics was reduced up to eight folds against the different cultures of E. coli by both chalcones. Among the two compounds, the i. e. 1-(3', 4,'5'-trimethoxyphenyl)-3-(3-Indyl)-prop-2-enone (6, Indl-2), a chalcone derivative of gallic acid (Indl-2) was better along with tetracycline (TET) worked synergistically and was found to inhibit efflux transporters as obvious by ethidium bromide efflux confirmed by ATPase assays and docking studies. In combination, Indl-2 kills the MDREC-KG4 cells, post-antibiotic effect (PAE) of TET was prolonged and mutant prevention concentration (MPC) of TET was also decreased. In-vivo studies revealed that Indl-2 reduces the concentration of TNF-α. In acute oral toxicity study, Indl-2 was non-toxic and well tolerated up-to dose of 2000 mg/kg. Perhaps, the study is going to report gallic acid derived chalcone as synergistic agent acting via inhibiting the primary efflux pumps.

Cellulose Functionalization Using N-Heterocyclic-Based Leaving Group Chemistry.

There has been continuous interest in developing novel activators that facilitate the functionalization of cellulosic materials. In this paper, we developed a strategy in which trisubstituted triazinium salts act as cellulose preactivators. As leaving groups, these triazinium salts utilize N-heterocycles (pyridine, imidazole, and nicotinic acid). Initially, we optimized the synthetic route for developing these novel cellulose preactivators (triazinium salts), whose structures were confirmed using NMR spectroscopy. The surface zeta potential of cellulose changed from a negative value to a positive one after preactivation due to the cationic nature of these preactivators. To enhance the scope of the study, we functionalized the cellulose-preactivated materials with a series of amine- or hydroxy-containing aliphatic and aromatic hydrocarbons, nucleophilic amino acids (cysteine), colorants (2-aminoanthraquinone and 2-amino-3-methyl-anthraquinone), and biopolymer (zein protein). The treated samples were analyzed using FTIR, time-gated Raman spectroscopy, and reflection spectroscopy, and the success of the functionalization process was validated. To widen the scope of such chemistries, we synthesized four reactive agents containing N-heterocyclic-based leaving groups (pyridine and nicotinic acid) and successfully functionalized cellulose with them in one step. The proposed single- and two-step functionalization approaches will provide opportunities for chemically linking various chemical compounds to cellulose for different applications.

Rapid metabolic fingerprinting with the aid of chemometric models to identify authenticity of natural medicines: Turmeric, Ocimum, and Withania somnifera study.

Herbal medicines are popular natural medicines that have been used for decades. The use of alternative medicines continues to expand rapidly across the world. The World Health Organization suggests that quality assessment of natural medicines is essential for any therapeutic or health care applications, as their therapeutic potential varies between different geographic origins, plant species, and varieties. Classification of herbal medicines based on a limited number of secondary metabolites is not an ideal approach. Their quality should be considered based on a complete metabolic profile, as their pharmacological activity is not due to a few specific secondary metabolites but rather a larger group of bioactive compounds. A holistic and integrative approach using rapid and nondestructive analytical strategies for the screening of herbal medicines is required for robust characterization. In this study, a rapid and effective quality assessment system for geographical traceability, species, and variety-specific authenticity of the widely used natural medicines turmeric, Ocimum, and Withania somnifera was investigated using Fourier transform near-infrared (FT-NIR) spectroscopy-based metabolic fingerprinting. Four different geographical origins of turmeric, five different Ocimum species, and three different varieties of roots and leaves of Withania somnifera were studied with the aid of machine learning approaches. Extremely good discrimination (R2 > 0.98, Q2 > 0.97, and accuracy = 1.0) with sensitivity and specificity of 100% was achieved using this metabolic fingerprinting strategy. Our study demonstrated that FT-NIR-based rapid metabolic fingerprinting can be used as a robust analytical method to authenticate several important medicinal herbs.

In vitro production of steroidal saponin, total phenols and antioxidant activity in callus suspension culture of Paris polyphylla Smith: an important Himalayan medicinal plant.

Paris polyphylla Smith (Melanthiaceae) family, which is native to the Himalayan region, has received a lot of attention recently due to its extensive history of usage in traditional medicine. The production of steroidal saponin from callus suspension cultures of P. polyphylla was observed in the current study. The current study attempted to develop a P. polyphylla plant callus suspension culture through optimization of cultivation technique for callus suspension, quantification of total phenolic components and estimation of the extract's antioxidant activity. A light-yellow callus was formed within six weeks of cultivating rhizomes on Murashige and Skoog (MS) media supplemented with Thidiazuron (TDZ). Furthermore, the effect of TDZ, Methyl Jasmonate (MeJA), and Yeast Extract (YE) on callus growth, steroidal saponin (dioscin and diosgenin), total phenolic content, total flavonoids, total tannin, and total antioxidant activity was also measured. The medium containing 0.5 µM TDZ depicted the maximum callus biomass (2.98 g fresh weight). Significantly high phenolic and tannin content was observed in the MS medium containing 50 µM MeJA, whereas, no significant increase was observed in total tannin production in any treatment. Three in vitro assays, DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis (3-ethylbenzothiazoline- 6-sulfonic acid)) and FRAP (ferric ion reducing antioxidant potential) and FC (Folin-Ciocalteu), were used to assess antioxidant potential of callus. Maximum antioxidant analysis reported in 1.0 µM TDZ (6.89 mM AAE/100 g) containing medium followed by 50 µM MeJA (6.44 mM AAE/100 g). The HPLC analysis showed a high presence of dioscin and diosgenin (5.43% and 21.09%, respectively) compared to the wild sample (2.56% and 15.05%, respectively). According to the results, callus produced on media supplemented with 50 µM MeJA have significant phenolic contents and elevated antioxidant activity; nevertheless, callus growth was greater in the presence of 0.5 µM TDZ. The findings of the current study have commercial implications since greater biomass production will result in active phytochemicals that the pharmaceutical and nutraceutical sectors are in need desperately.

Imidazoles as Serotonin Receptor Modulators for Treatment of Depression: Structural Insights and Structure-Activity Relationship Studies.

Serotoninergic signaling is identified as a crucial player in psychiatric disorders (notably depression), presenting it as a significant therapeutic target for treating such conditions. Inhibitors of serotoninergic signaling (especially selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI)) are prominently selected as first-line therapy for the treatment of depression, which benefits via increasing low serotonin levels and norepinephrine by blocking serotonin/norepinephrine reuptake and thereby increasing activity. While developing newer heterocyclic scaffolds to target/modulate the serotonergic systems, imidazole-bearing pharmacophores have emerged. The imidazole-derived pharmacophore already demonstrated unique structural characteristics and an electron-rich environment, ultimately resulting in a diverse range of bioactivities. Therefore, the current manuscript discloses such a specific modification and structural activity relationship (SAR) of attempted derivatization in terms of the serotonergic efficacy of the resultant inhibitor. We also featured a landscape of imidazole-based development, focusing on SAR studies against the serotoninergic system to target depression. This study covers the recent advancements in synthetic methodologies for imidazole derivatives and the development of new molecules having antidepressant activity via modulating serotonergic systems, along with their SAR studies. The focus of the study is to provide structural insights into imidazole-based derivatives as serotonergic system modulators for the treatment of depression.

Light-Driven Depolymerization of Cellulosic Biomass into Hydrocarbons.

Cellulose and hemicellulose are the main constituents of lignocellulosic biomass. Chemical derivatization of lignocellulosic biomass leads to a range of C5 and C6 organic compounds. These C5 and C6 compounds are valuable precursors (or fine chemicals) for developing sustainable chemical processes. Therefore, depolymerization of cellulose and hemicellulose is essential, leading to the development of various materials that have applications in biomaterial industries. However, most depolymerized processes for cellulose have limited success because of its structural quality: crystallinity, high hydrogen-bond networking, and mild solubility in organic and water. As a result, various chemical treatments, acidic (mineral or solid acids) and photocatalysis, have developed. One of the significant shortcomings of acidic treatment is that the requirement for high temperatures increases the commercial end cost (energy) and hampers product selectivity. For example, a catalyst with prolonged exposure to high temperatures damages the catalyst surface over time; therefore, it cannot be used for iterative cycles. Photocatalysts provide ample application to overcome such flaws as they do not require high temperatures to perform efficient catalysis. Various photocatalysts have shown efficient cellulosic biomass conversion into its C6 and C5 hydrocarbons and the production of hydrogen (as a green energy component). For example, TiO2-based photocatalysts are the most studied for biomass valorization. Herein, we discussed the feasibility of a photocatalyst with application to cellulosic biomass hydrolysis.

MicroRNAs-Based Theranostics against Anesthetic-Induced Neurotoxicity.

Various clinical reports indicate prolonged exposure to general anesthetic-induced neurotoxicity (in vitro and in vivo). Behavior changes (memory and cognition) are compilations commonly cited with general anesthetics. The ability of miRNAs to modulate gene expression, thereby selectively altering cellular functions, remains one of the emerging techniques in the recent decade. Importantly, engineered miRNAs (which are of the two categories, i.e., agomir and antagomir) to an extent found to mitigate neurotoxicity. Utilizing pre-designed synthetic miRNA oligos would be an ideal analeptic approach for intervention based on indicative parameters. This review demonstrates engineered miRNA's potential as prophylactics and/or therapeutics minimizing the general anesthetics-induced neurotoxicity. Furthermore, we share our thoughts regarding the current challenges and feasibility of using miRNAs as therapeutic agents to counteract the adverse neurological effects. Moreover, we discuss the scientific status and updates on the novel neuro-miRNAs related to therapy against neurotoxicity induced by amyloid beta (Aß) and Parkinson's disease (PD).

Fabrication of Colored Polymeric Membrane Using Clay-Based Nano Pigments of Safranin O (SO) Dye.

In the present work, a novel methodology was developed for the fabrication of clay-based nano pigments with enhanced thermal stability and used further as a colorant to prepare polymeric membranes. Initially, the batch extraction studies were performed to analyze the maximum adsorption of Safranin O (SO) dye onto pristine montmorillonite (Mt) and organo montmorillonite (OMt) by varying different parameters like pH, contact time, and concentration. It was confirmed from batch extraction studies that the adsorption efficacy of pristine Mt for SO was found to be more than OMt due to their negatively charged surface. Clay-based nano pigments were fabricated by considering the optimized condition where the maximum uptake of SO was observed and further characterized by XRD, FTIR, TGA, and SEM techniques. XRD studies confirmed the intercalation of SO dye while FTIR spectra revealed surface interaction of the dye with Mt/OMt. TGA studies showed that the clay-based nano pigments had more thermal stability than pure SO. Nano pigments were used as colorants to prepare thin, transparent, and homogeneously dispersed polymeric membranes through the solvent casting method. XRD studies of the polymeric membrane confirmed that the intercalation of poly methylmethacrylate (PMMA) into the interlayer of clay increases interlayer spacing, which was further confirmed by the TEM analysis. The mechanical properties of the PMMA polymeric membrane were also enhanced after the dispersion of clay-based nano pigments.

Electro-organic synthesis of C-5 sulfenylated amino uracils: Optimization and exploring topoisomerase-I based anti-cancer profile.

Cancer is spreading worldwide and is one of the leading causes of death. The use of existing chemotherapeutic agents is frequently limited due to side effects. As a result, it is critical to investigate new agents for cancer treatment. In this context, we developed an electrochemical method for the synthesis of a series of thiol-linked pyrimidine derivatives (3a-3p) and explored their anti-cancer potential. The biological profile of the synthesized compounds was evaluated against breast (MDAMB-231 and MCF-7) and colorectal (HCT-116) cancer cell lines. 3b and 3d emerged to be the most potent agents, with IC50 values ranging between 0.98 to 2.45 µM. Target delineation studies followed by secondary anticancer parameters were evaluated for most potent compounds, 3b and 3d. The analysis revealed compounds possess DNA intercalation potential and selective inhibition towards human topoisomerase (hTopo1). The analysis was further corroborated by DNA binding studies and in silico-based molecular modeling studies that validated the intercalating binding mode between the compounds and the DNA.

Dual targeted 2-Benzylideneindanone pendant hydroxamic acid group exhibits selective HDAC6 inhibition along with tubulin stabilization effect.

Abnormal epigenetics has been recognised as an early event in tumour progression and aberrant acetylation of lysine in particular has been understood in tumorigenesis. Therefore, it has become an attractive target for anticancer drug development. However, HDAC inhibitors have limited success due to toxicity and drug resistance concerns. Present study deals with design and synthesis of bivalent indanone based HDAC6 and antitubulin ligands as anticancer agents. Two of the analogues 9 and 21 exhibited potent antiproliferative activities (IC50, 0.36-3.27 µM) and high potency against HDAC 6 enzyme. Compound 21 showed high selectivity against HDAC 6 while 9 exhibited low selectivity. Both the compounds also showed microtubule stabilization effects and moderate anti-inflammatory effect. Dual targeted anticancer agents with concomitant anti-inflammatory effects will be more attractive clinical candidates in future.

Synthesis of Nano Pigments Using Clay Minerals and Organic Dyes and Their Application as Colorants in Polymer Matrix.

A new generation of clay-based nano pigments has been introduced, providing the advantage of both inorganic pigments and organic dyes. These nano pigments have been synthesized through a stepwise procedure where, initially, an organic dye is adsorbed onto the surface of the adsorbent, and then dye adsorbed adsorbent is used as pigment for further applications. The objective of the current paper was to examine the interaction of non-biodegradable toxic dyes, Crystal Violet (CV) and Indigo Carmine (IC), with clay minerals (montmorillonite (Mt), vermiculite (Vt), and clay bentonite (Bent)) and their organically modified forms (OMt, OBent, and OVt) and to develop a novel methodology for the synthesis of the value-added products and clay-based nano pigments without creating second generation waste materials. In our observation, the uptake of CV was more intense onto pristine Mt, Bent, and Vt, and the uptake of IC was more onto OMt, OBent, and OVt. CV was found to be in the interlayer region of Mt and Bent, as supported by XRD data. Zeta potential values confirmed the presence of CV on their surface. In contrast, in the case of Vt and organically modified forms, the dye was found on the surface, confirmed by XRD and zeta potential values. In the case of indigo carmine, the dye was found only on the surface of pristine Mt, Bent, Vt, and organo Mt, Bent, Vt. During the interaction of CV and IC with clay and organoclays, intense violet and blue-colored solid residues were obtained (also known as clay-based nano pigments). The nano pigments were used as colorants in a poly (methyl-methacrylate) (PMMA) polymer matrix to form transparent polymer films.

Crosstalk between long noncoding RNA and microRNA in Cancer.

miRNAs and lncRNAs play a central role in cancer-associated gene regulations. The dysregulated expression of lncRNAs has been reported as a hallmark of cancer progression, acting as an independent prediction marker for an individual cancer patient. The interplay of miRNA and lncRNA decides the variation of tumorigenesis that could be mediated by acting as sponges for endogenous RNAs, regulating miRNA decay, mediating intra-chromosomal interactions, and modulating epigenetic components. This paper focuses on the influence of crosstalk between lncRNA and miRNA on cancer hallmarks such as epithelial-mesenchymal transition, hijacking cell death, metastasis, and invasion. Other cellular roles of crosstalks, such as neovascularization, vascular mimicry, and angiogenesis were also discussed. Additionally, we reviewed crosstalk mechanism with specific host immune responses and targeting interplay (between lncRNA and miRNA) in cancer diagnosis and management.

Design and Development of COX-II Inhibitors: Current Scenario and Future Perspective.

Innate inflammation beyond a threshold is a significant problem involved in cardiovascular diseases, cancer, and many other chronic conditions. Cyclooxygenase (COX) enzymes are key inflammatory markers as they catalyze prostaglandins production and are crucial for inflammation processes. While COX-I is constitutively expressed and is generally involved in "housekeeping" roles, the expression of the COX-II isoform is induced by the stimulation of different inflammatory cytokines and also promotes the further generation of pro-inflammatory cytokines and chemokines, which affect the prognosis of various diseases. Hence, COX-II is considered an important therapeutic target for drug development against inflammation-related illnesses. Several selective COX-II inhibitors with safe gastric safety profiles features that do not cause gastrointestinal complications associated with classic anti-inflammatory drugs have been developed. Nevertheless, there is mounting evidence of cardiovascular side effects from COX-II inhibitors that resulted in the withdrawal of market-approved anti-COX-II drugs. This necessitates the development of COX-II inhibitors that not only exhibit inhibit potency but also are free of side effects. Probing the scaffold diversity of known inhibitors is vital to achieving this goal. A systematic review and discussion on the scaffold diversity of COX inhibitors are still limited. To address this gap, herein we present an overview of chemical structures and inhibitory activity of different scaffolds of known COX-II inhibitors. The insights from this article could be helpful in seeding the development of next-generation COX-II inhibitors.

An Investigative Study on the Structural, Thermal and Mechanical Properties of Clay-Based PVC Polymer Composite Films.

The present study aims to explore the impact of pristine and surfactant-modified clays (montmorillonite, bentonite and vermiculite) on the thermomechanical properties of a poly (vinyl chloride) (PVC) polymer film. Initially, clay was modified by employing the ion exchange method. The modification of clay minerals was confirmed by the XRD pattern and thermogravimetric analysis. Pristine PVC polymer film and clay (montmorillonite, bentonite and vermiculite)-based PVC polymer composite films were fabricated using solution casting. The ideal dispersion of surfactant-modified organo-clays was observed in the PVC polymer matrix due to the hydrophobic nature of modified clays. The resultant pure polymer film and clay polymer composite film were characterized using XRD and TGA, and their mechanical properties were determined using a tensile strength tester and Durometer. From the XRD pattern, the intercalation of the PVC polymer film was found in the interlayer of organo-clay while exfoliation or partial intercalation and exfoliation were observed for pristine clay mineral-based PVC polymer composite films. Thermal analysis indicated a lowering of the decomposition temperature of the composite film as clay promotes the thermal degradation temperature of PVC. Improvement in the tensile strength and hardness was found to be more frequent in the case of organo-clay-based PVC polymer films, which is only due to the hydrophobic nature of organ clays, resulting in greater compatibility with the polymer matrix.

Chitosan Nanoparticles-Based Cancer Drug Delivery: Application and Challenges.

Chitin is the second most abundant biopolymer consisting of N-acetylglucosamine units and is primarily derived from the shells of marine crustaceans and the cell walls of organisms (such as bacteria, fungi, and algae). Being a biopolymer, its materialistic properties, such as biodegradability, and biocompatibility, make it a suitable choice for biomedical applications. Similarly, its deacetylated derivative, chitosan, exhibits similar biocompatibility and biodegradability properties, making it a suitable support material for biomedical applications. Furthermore, it has intrinsic material properties such as antioxidant, antibacterial, and antitumor. Population studies have projected nearly 12 million cancer patients across the globe, where most will be suffering from solid tumors. One of the shortcomings of potent anticancer drugs is finding a suitable cellular delivery material or system. Therefore, identifying new drug carriers to achieve effective anticancer therapy is becoming essential. This paper focuses on the strategies implemented using chitin and chitosan biopolymers in drug delivery for cancer treatment.

Estrogen Receptor-α Targeting: PROTACs, SNIPERs, Peptide-PROTACs, Antibody Conjugated PROTACs and SNIPERs.

Targeting selective estrogen subtype receptors through typical medicinal chemistry approaches is based on occupancy-driven pharmacology. In occupancy-driven pharmacology, molecules are developed in order to inhibit the protein of interest (POI), and their popularity is based on their virtue of faster kinetics. However, such approaches have intrinsic flaws, such as pico-to-nanomolar range binding affinity and continuous dosage after a time interval for sustained inhibition of POI. These shortcomings were addressed by event-driven pharmacology-based approaches, which degrade the POI rather than inhibit it. One such example is PROTACs (Proteolysis targeting chimeras), which has become one of the highly successful strategies of event-driven pharmacology (pharmacology that does the degradation of POI and diminishes its functions). The selective targeting of estrogen receptor subtypes is always challenging for chemical biologists and medicinal chemists. Specifically, estrogen receptor α (ER-α) is expressed in nearly 70% of breast cancer and commonly overexpressed in ovarian, prostate, colon, and endometrial cancer. Therefore, conventional hormonal therapies are most prescribed to patients with ER + cancers. However, on prolonged use, resistance commonly developed against these therapies, which led to selective estrogen receptor degrader (SERD) becoming the first-line drug for metastatic ER + breast cancer. The SERD success shows that removing cellular ER-α is a promising approach to overcoming endocrine resistance. Depending on the mechanism of degradation of ER-α, various types of strategies of developed.

Chitosan Nanoparticle Encapsulation of Antibacterial Essential Oils.

Chitosan is the most suitable encapsulation polymer because of its natural abundance, biodegradability, and surface functional groups in the form of free NH2 groups. The presence of NH2 groups allows for the facile grafting of functionalized molecules onto the chitosan surface, resulting in multifunctional materialistic applications. Quaternization of chitosan's free amino is one of the typical chemical modifications commonly achieved under acidic conditions. This quaternization improves its ionic character, making it ready for ionic-ionic surface modification. Although the cationic nature of chitosan alone exhibits antibacterial activity because of its interaction with negatively-charged bacterial membranes, the nanoscale size of chitosan further amplifies its antibiofilm activity. Additionally, the researcher used chitosan nanoparticles as polymeric materials to encapsulate antibiofilm agents (such as antibiotics and natural phytochemicals), serving as an excellent strategy to combat biofilm-based secondary infections. This paper provided a summary of available carbohydrate-based biopolymers as antibiofilm materials. Furthermore, the paper focuses on chitosan nanoparticle-based encapsulation of basil essential oil (Ocimum basilicum), mandarin essential oil (Citrus reticulata), Carum copticum essential oil ("Ajwain"), dill plant seed essential oil (Anethum graveolens), peppermint oil (Mentha piperita), green tea oil (Camellia sinensis), cardamom essential oil, clove essential oil (Eugenia caryophyllata), cumin seed essential oil (Cuminum cyminum), lemongrass essential oil (Cymbopogon commutatus), summer savory essential oil (Satureja hortensis), thyme essential oil, cinnamomum essential oil (Cinnamomum zeylanicum), and nettle essential oil (Urtica dioica). Additionally, chitosan nanoparticles are used for the encapsulation of the major essential components carvacrol and cinnamaldehyde, the encapsulation of an oil-in-water nanoemulsion of eucalyptus oil (Eucalyptus globulus), the encapsulation of a mandarin essential oil nanoemulsion, and the electrospinning nanofiber of collagen hydrolysate-chitosan with lemon balm (Melissa officinalis) and dill (Anethum graveolens) essential oil.

Anti-inflammatory, anti-oxidant and cardio-protective properties of novel fluorophenyl benzimidazole in L-NAME-induced hypertensive rats.

BACKGROUND: Chronic inflammation and oxidative stress play important role in development of hypertension. Recently, we have reported novel fluorophenyl benzimidazole (FPD) for vasorelaxation and antihypertensive activity in SHRs. The present study envisaged the anti-inflammatory, anti-oxidant and cardio-protective properties of FPD in L-NAME model of hypertension with special emphasis on reversal of vascular remodeling, gene expression and restoration of hemodynamic. METHODS: Antihypertensive activity of FPD was evaluated in L-NAME treated Wistar rats, and the parameters studied were anti-inflammatory activity, histomorphological changes, gene expression profile and anti-oxidant properties. RESULTS: FPD at 50 and 100 mg kg-1 once daily for 15 days significantly reduced SBP, DBP and MAP in L-NAME treated rats and the values were well comparable to vehicle control group. Further, FPD treatment showed a significant increase in hepatic GSH content, SOD, catalase activity, decreased MDA level and restoration of pro and anti-inflammatory cytokine levels. The mRNA expression profile of genes associated with regulation of vascular tone, remodeling and inflammation showed a significant level of alteration by chronic L-NAME treatment and was dose-dependently restored upon treatment with FPD. Further, FPD treatment restored serum lipid profile, CK, CK-MB and LDH level and also reversed the histomorphological changes like intimal wall thickening, hyperplasia of cardiomyocytes and ventricular wall thickening. CONCLUSIONS: Taken together, FPD produced potent antihypertensive activity in L-NAME model through vasorelaxation, anti-oxidative and anti-inflammatory properties leading to restoration of serum lipid profile, cardiac biomarker, expression profile of target genes and reversal of histomorphological changes.

Synthesis, Molecular Docking, and 2D-QSAR Modeling of Quinoxaline Derivatives as Potent Anticancer Agents against Triple-negative Breast Cancer.

BACKGROUND: Breast carcinomas aka triple-negative breast cancers (TNBC) are one of the most complex and aggressive forms of cancers in females. Recently, studies have shown that these carcinomas are resistant to hormone-targeted therapies, which makes it a priority to search for effective and potential anticancer drugs. The present study aimed to synthesize and develop the 2Dquantitative structural activity relationship model (QSAR) of quinoxaline derivatives as a potential anticancer agent. METHODS: Quinoxaline derivatives were designed and synthesized (8a-8i and 9a-9d) and the 2DQSAR model against TNBC was developed using VLife MDS v4.4. The anticancer activity was investigated against the TNBC MDA-MB-231 cell line using an MTT cytotoxicity assay. Molecular docking studies along with the estimation of ADMET parameters were done using Discovery Studio. The most potent compound was docked against the ß-tubulin protein target (PDB: 4O2B), using the Autodock Vina v0.8 program. RESULTS: Eleven derivatives of quinoxaline were designed and synthesized (8a-8i and 9a-9d) and a 2D-QSAR model was developed against the TNBC MDA-MB231 cell line. The regression coefficient values for the training set were (r2) 0.78 and (q2) 0.71. Further, external test set regression (pred_r2) was 0.68. Five molecular descriptors viz., energy dispersive (Epsilon3), protein-coding gene (T_T_C_6), molecular force field (MMFF_6), most hydrophobic hydrophilic distance (XA), and Zcomp Dipole were identified. After ADMET, the best analog 8a showed the best activity against the TNBC cell line. The best-predicted hit '8a' was found to bind within the active site of the ß- tubulin protein target. CONCLUSION: The newly synthesized quinoxaline compounds could serve as potent leads for the development of novel anti-cancer agents against TNBC.