Preclinical determination of wound-healing activity of halibut oil cream in rat model of burn wound.

This study investigated the effects of halibut oil cream, containing omega-3 fatty acids, vitamins A and D, and hydroxyproline, on burn wound healing in rats. Acute dermal toxicity tests confirmed its nontoxicity. Wistar rats were divided into five groups: a control, a positive control treated with silver sulfadiazine 1% (SSD), and three groups treated with 3%, 9%, and 27% halibut oil cream Formulation (HBOF). The SSD and HBOF groups showed significant healing improvements compared to the control. Histopathological analysis indicated increased collagen production in the HBOF groups, suggesting halibut oil cream's potential as a topical treatment for burn wounds.

Envisaging Structural Insight of a Terminally Protected Proline Dipeptide by Raman Spectroscopy and Density Functional Theory Analyses.

The proline residue in a protein sequence generates constraints to its secondary structure as the associated torsion angles become a part of the heterocyclic ring. It becomes more significant when two consecutive proline residues link via amide linkage and produce additional configurational constraint to a protein's folding and stability. In the current manuscript we have illustrated conformation preference of a novel dipeptide, (R)-tert-butyl 2-((S)-2-(methoxycarbonyl)pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate. The dipeptide crystallized in the orthorhombic crystalline state and produced rod-shaped macroscopic material. The analysis of the crystal coordinates showed dihedral angles (φ, ψ) of the interlinked amide groups as (+72°, -147°) and the dihedral angles (φ, ψ) produced with the next carbonyl were (-68°, +151°), indicating polyglycine II (PGII) and polyproline II (PPII)-like helix states at the N- and C-terminals, respectively. These two states, PGII and PPII, are mirror image configurations and are expected to produce similar vibration bands from the associated carbonyl groups. However, the unique atomic arrangement in the molecule produces three carbonyl groups and one of them was very specific, being part of the main peptide linkage that connects both the pyrrolidine rings. The carbonyl group in the peptide bond exhibited a Raman vibration frequency at ∼1642 cm-1 and is considered a signatory Raman marker band for the peptide bond linking two heterochiral proline residues. The carbonyl group (t-Boc) at the N-terminal of the peptide showed a characteristic vibration at ∼1685 cm-1 and the C-terminal carbonyl group as a part of the ester showed a vibration signature at a significantly high frequency (1746 cm-1). Conformation analyses performed with density functional theory (DFT) calculations depicted that the dipeptide was stabilized in vacuum with dihedral angles (+72°, -154°) and (-72°, +151°) at the N- and C-terminals, respectively. Molecular dynamics (MD) simulation also showed that the peptide conformation having dihedral angles around (+75°, -150°) and (-75°, +150°) at the N- and C-terminals, respectively, was reasonably stable in water. Due to unique absence of the amide N-H, the peptide was ineffective in forming any intramolecular hydrogen bonding. MD investigation, however, revealed an intermolecular hydrogen bonding interaction with the water molecules, leading to its stability in aqueous solution. Metadynamics simulation analysis of the dipeptide in water also supported the PGII-PPII-like conformation at the N- and C-terminals, respectively, as the energetically stable conformation among the other possible combinations of conformations. The possible electronic transitions along with the HOMO-LUMO analysis further depicted the stability of the dipeptide in water and their possible absorption pattern. Time-dependent density functional theory (TDDFT) analysis showed strong negative rotatory strength of the dipeptide around 210 nm in water and acetonitrile, and it could be the source of experimentally observed high-amplitude negative absorption in the circular dichroism (CD) spectra around 200-203 nm. The very weak positive band (signature) in the region at ∼228 nm in CD spectra could also be correlated to the positive rotatory strength at 228 nm observed in ECD. To test the effect of such a dipeptide on a living cell, an MTT assay was performed and the result indicated no cytotoxic effect toward human hepatocellular carcinoma Hep G2 cancer cell lines.

ZnI2-Catalyzed Diastereoselective [4 + 2] Cycloadditions of ß,γ-Unsaturated α-Ketothioesters with Olefins.

The potential of ß,γ-unsaturated α-ketothioesters participating in hetero-Diels-Alder reaction has remained unexplored. We report herein the first study of a ZnI2-catalyzed highly diastereoselective inverse electron demand hetero-Diels-Alder reaction of ß,γ-unsaturated α-ketothioesters with olefins to access highly substituted 3,4-dihydro-2H-pyrans. All the reactions proceed with cis-selectivity in moderate to excellent yields. Under similar reaction conditions, terminal alkynes undergo direct conjugate 1,4-addition to yield δ,ε-acetylenic α-ketothioesters. Furthermore, the utility of these cycloadducts has been demonstrated by an NBS-MeOH mediated stereospecific efficient access to fully substituted pyran rings. The product bromoethers undergo E2 elimination with DBU, resulting in substituted 3,6-dihydro-2H-pyrans. In addition, the thioester moiety of the products has been used for further transformations, such as amidations and Fukuyama coupling reactions.

Stability and binding interaction of bilirubin on a gold nano-surface: steady state fluorescence and FT-IR investigation.

A gold nanoparticle exhibits strong absorption and emission due to its unique physical geometry and surface plasmon resonance phenomena. A further modification with organic molecules makes it more appropriate for biological applications. The current manuscript illustrated the optical behavior and stability of bilirubin (BR) coated gold (AuBR) nanoparticles, using BR itself as a reducing agent. In addition, FT-IR and steady state fluorescence measurements were performed to illustrate the binding interaction of BR with the Au(III) ion and the nanoparticles. BR showed a strong affinity towards Au(III) and the measured binding constant was ∼4.3 × 10(5) M(-1). It caused reduction of the Au(III) ion and rendered the formation of cubic face centered AuBR nanoparticles, which were ∼20 nm in diameter. The particles were stabilized as BR was bound to the gold nanoparticle surface, which was confirmed by FT-IR measurement. An intense carboxyl C=O stretching vibration at 1695 cm(-1) was observed for the BR powder but was absent for the AuBR nanoparticles. However, two weak bands at ∼1563 and 1391 cm(-1), presumably due to the asymmetric and symmetric stretching vibrations of the carboxylate form (COO(-)), were found for the AuBR nanoparticles. A stretching vibration of lactam C[double bond, length as m-dash]O appeared at 1645 cm(-1) for BR and the band was shifted to 1647 cm(-1) for the AuBR nanoparticles. The stretching modes of pyrrole N-H and lactam N-H were detected at 3406 cm(-1) and 3267 cm(-1), respectively, for BR. However, the pyrrole N-H band shifted to 3446 cm(-1) and became broader for the AuBR nanoparticles. The observed blue shift in the lactam C[double bond, length as m-dash]O and N-H vibrations of the AuBR nanoparticles indicated a weakening/absence of internal hydrogen bonds between the carboxyl groups and the four N-H bonds in the BR moiety. The binding of BR to the surface provides great stability to the nanoparticles, which remained monodispersed in the large pH range (pH 4 to 12) for more than a month. However, under acidic pH conditions the particles associated to form bigger particles and the plasmon resonance band shifted as they grew; the plasmon resonance band shifted from 525 nm (at pH 7.0) to 555 nm (at pH 3.0). The particles also remained stable in the presence of a higher concentration of salt (KCl and NaCl) in the dispersing media.

Non-thermal plasma mitigation of low concentration of air pollutants: removal of isopropyl alcohol using transition metal-oxide integration.

The present work studied the decomposition of isopropyl alcohol (IPA), widely used in chemical industries and households, in a packed-bed dielectric barrier discharge (DBD) plasma reactor. Metal oxide (MOx) coated on γ-Al2O3 (M = Cu, Mn, Co) was utilized for packing. The plasma-packed mode was a likely alternative to the conventional removal techniques, as it aids the conversion of dilute concentrations of IPA to CO and CO2 at ambient conditions (room temperature and atmospheric pressure). The mean electron energy calculations suggest that electrons with higher energy are generated when the discharge zone is packed with catalysts. When comparing IPA conversion (input concentration of 25 ppm) for no packing mode and MOx/γ-Al2O3 coupled plasma mode, the latter method enhances conversion to greater than 90% at an applied voltage of 18 kV. Also, MOx/γ-Al2O3 showed the highest selectivity to CO2 (70%) compared to plasma-only mode (45%). The metal-oxide layer provides the necessary catalytic surface facilitating the oxidation of IPA to COx through active oxygen species or the interaction of surface hydroxyl groups. The use of MOx/γ-Al2O3 resulted in about 90% carbon balance and reduced ozone generation, demonstrating the significance of integrating metal oxide to achieve efficient conversion and maximal selectivity towards the desired products.

Local Anesthesia Onset and Pain Perception in Hemophilic and Thalassemic Conditions.

The study aims to evaluate and compare the onset of local anesthesia (LA) and pain perception during endodontic treatment in hemophilic and thalassemic patients. Methods: The study included 90 patients with symptomatic irreversible pulpitis of the mandibular molars. Three groups (n = 30 in each group) were included. Group 1: hemophilic patients; group 2: thalassemic patients; and group 3: individuals without any systemic diseases. Onset of LA and visual analogue scale (VAS) scores was recorded immediately after the administration of local anesthesia, during the pulp exposure procedure, and during canal instrumentation, and were compared between the three groups. Frequency distribution, ANOVA, and linear regression analysis (p < 0.05) were applied. Results: The mean onset time was 46 ± 34 s in the hemophilic group, 42 ± 23 s in the thalassemic group, and 38 ± 12 s in controls, but the differences were statistically insignificant. After LA administration (LA-VAS), all three groups experienced a statistically significant reduction in pain (p = 0.048). On pulp exposure (PE-VAS) (p = 0.82) and during canal instrumentation (CI-VAS) (p = 0.55), there was no statistically significant difference in pain perception between the groups. The coefficients indicate a positive correlation between the VAS and onset time, indicating a positive reduction in the VAS following the administration of LA. Conclusions: Hemophilic patients exhibited a clinically longer average onset time for LA. However, the difference among the three groups with regard to the overall pain perception after LA administration, during and after pulp exposure, and during canal instrumentation was statistically insignificant.

Design of a self-cleanable multilevel anticounterfeiting interface through covalent chemical modulation.

Counterfeit products have posed a significant threat to consumers safety and the global economy. To address this issue, extensive studies have been exploring the use of coatings with unclonable, microscale features for authentication purposes. However, the ease of readout, and the stability of these features against water, deposited dust, and wear, which are required for practical use, remain challenging. Here we report a novel class of chemically functionalizable coatings with a combination of a physically unclonable porous topography and distinct physiochemical properties (e.g., fluorescence, water wettability, and water adhesion) obtained through orthogonal chemical modifications (i.e., 1,4-conjugate addition reaction and Schiff-base reaction at ambient conditions). Unprecedentedly, a self-cleanable and physically unclonable coating is introduced to develop a multilevel anticounterfeiting interface. We demonstrate that the authentication of the fluorescent porous topography can be verified using deep learning. More importantly, the spatially selective chemical modifications can be read with the naked eye via underwater exposure and UV light illumination. Overall, the results reported in this work provide a facile basis for designing functional surfaces capable of independent and multilevel decryption of authenticity.

The International Classification of Functioning, Disability and Health Core Set for deafblindness. Part I: a systematic review of outcome measures.

INTRODUCTION: The International Classification of Functioning, Disability, and Health (ICF), developed by the World Health Organization, is a classification framework that focuses on the health and functioning of people with disabilities. As part of an ICF Core Set development, four studies need to be conducted, one of which is a systematic review. This study presents part 1 of the systematic review that aims to describe the outcome measures identified in the literature related to functioning in individuals with deafblindness. EVIDENCE ACQUISITION: The research team screened articles from eight scientific databases, three journals, and Google Scholar (March 2011 to September 2022). Articles were included if they studied individuals with deafblindness aged 18 and older. Studies that examined genetics or laboratory experiments involving animals were excluded. Data were extracted into a logbook with key descriptors such as study location and design, age of study population, and instruments/outcome measures used, which were further categorized into one of the following types: 1) standardized; 2) patient-reported measures, standardized (PT-S); 3) patient-reported measures, not standardized (PT-not S); 4) health professional, reported measures, standardized (HP-S); 5) Technical measures; 6) other measures (parent-reported standardized and laboratory measures). EVIDENCE SYNTHESIS: The review included 147 studies, of which most were conducted in Europe (47.6%) and North America (27.9%). Of the 314 identified outcome measures, 57 were Standardized, 59 were Patient Reported-Standardized (PT-S), 178 were patient reported non-standardized (PT-Not S) variables, 11 were health professional reported, standardized, five were technical, and four were classified as other measures. CONCLUSIONS: Most instruments measured functioning in daily activities and the mental health of individuals with deafblindness. Three deafblind-specific instruments were identified in this study, highlighting the need for more deafblind-specific instruments to be developed and utilized in research.

Electrocatalytic Water Oxidation: An Overview With an Example of Translation From Lab to Market.

Water oxidation has become very popular due to its prime role in water splitting and metal-air batteries. Thus, the development of efficient, abundant, and economical catalysts, as well as electrode design, is very demanding today. In this review, we have discussed the principles of electrocatalytic water oxidation reaction (WOR), the electrocatalyst and electrode design strategies for the most efficient results, and recent advancement in the oxygen evolution reaction (OER) catalyst design. Finally, we have discussed the use of OER in the Oxygen Maker (OM) design with the example of OM REDOX by Solaire Initiative Private Ltd. The review clearly summarizes the future directions and applications for sustainable energy utilization with the help of water splitting and the way forward to develop better cell designs with electrodes and catalysts for practical applications. We hope this review will offer a basic understanding of the OER process and WOR in general along with the standard parameters to evaluate the performance and encourage more WOR-based profound innovations to make their way from the lab to the market following the example of OM REDOX.

Multiplexed Covalent Patterns on Double-Reactive Porous Coating.

We have conceptualized and demonstrated an approach based on the combination of hydrophobicity, a substrate-independent dip coating as porous material with double residual chemical reactivities for implementing multiplexed, miniaturized and unclonable bulk-infused patterns of different fluorophores following distinct reaction pathways. The embedded hydrophobicity (∼102°) restricted the unwanted spreading of beaded aqueous ink on the coating. The constructions of micropatterns on porous dip-coating via ink-jet printing or microchannel cantilever spotting offered orthogonal read-out and remained readable even after removal of the exterior of the coating.

Abrasion tolerant, non-stretchable and super-water-repellent conductive & ultrasensitive pattern for identifying slow, fast, weak and strong human motions under diverse conditions.

The conversion of mechanical deformation into electrical signals is a widely used principle for various relevant applications. Facile & scalable fabrication, ultrahigh-sensitivity, low-response time and uninterrupted performance under severe conditions are hallmarks of an efficient strain-sensor that would be suitable for realistic application. In the past, various approaches were introduced to achieve high gauge factor-mainly associated with a large tensile deformation. But, in reality, a flexible strain sensor that displays a high gauge factor at low applied strain and remains efficient under practically relevant diverse and challenging conditions would be more appropriate for unambiguous and effective monitoring of human motions and other relevant applications. But, a low-strain sensor with ultrahigh sensitivity and durability is yet to be introduced in the literature. Here, a metal-free, chemically reactive and conductive ink is unprecedentedly introduced following a 1,4-conjugate addition reaction. Furthermore, a strategic integration of a chemically reactive porous paper with the prepared conductive ink allowed the development of a chemically reactive and conductive interface that allowed desired post covalent modification with selected alkylamines under ambient conditions. Taking advantage of the spatially selective deposition of the prepared ink on chemically recative paper and the ability of post covalent modification of the prepared ink, an abrasion tolerant superhydrophobic & conductive patterned interface was developed for achieving a low-strain (below 0.2%) based flexible strain sensor with an ultrahigh sensitivity (gauge factor ∼18 300) and low response time (8 ms). The external low-strain induced cracks on the flexible & durable superhydrophobic and conductive patterned interface provided a facile basis for real-time & wireless monitoring of slow, fast, weak and strong human motions & expressions-under diverse conditions, including continuous aqueous exposures, physical abrasions etc.

Covalently Modulated and Transiently Visible Writing: Rational Association of Two Extremes of Water Wettabilities.

Anticounterfeiting measures are of ever-increasing importance in society, e.g., for securing the authenticity of and the proof of origin for medical drugs. Here, an arms race of counterfeiters and valid manufacturers is taking place, resulting in the need of hard-to-forget, yet easy-to-read out marks. Anticounterfeiting measures based on micropatterns-while being attractive for their need in not widely available printing methods while still being easily read out with fairly common basic optical equipment-are often limited by being too easy to be destroyed by wear or handling. Here, nature-inspired wettability is rationally exploited for developing an unprecedented anticounterfeiting method, where hidden information can be only identified under direct exposures to an aqueous phase or mist and disappears again on air-drying the interface. A chemically reactive and hierarchically featured dip coating, capable of spatially selective covalent modification with primary amine containing small molecules, is developed for abrasion-tolerant patterning interfaces with two extremes of water wettabilities, i.e., superhydrophilicity and superhydrophobicity. Arbitrary handwriting with glucamine followed by chemical modification with octadecylamine, provided "invisible" text on the synthesized interface. The glucamine-treated region selectively becomes optically transparent and superhydrophilic due to rapid infiltration of the aqueous phase on exposure to liquid water or mist. The remaining interface remains opaque and superhydrophobic due to metastable entrapment of air. The hidden text became transiently and reversibly visible by the naked eye under exposure to liquid water/mist. Furthermore, microchannel-cantilever spotting (µCS) is adopted for demonstrating well-defined chemical patterning on the microscale. These patterns are at the same time highly resistant against wear and scratching because of the bulk functionalization, retaining the wetting properties (and thus pattern readout) even on serious abrasion. Such a simple synthesis of spatially controlled, direct, and covalently modulated wettability could be useful for various applied and fundamental contexts.

Order, Disorder, and Reorder State of Lysozyme: Aggregation Mechanism by Raman Spectroscopy.

Lysozyme, like many other well-folded globular proteins, under stressful conditions produces nanoscale oligomer assembly and amyloid-like fibrillar aggregates. With engaging Raman microscopy, we made a critical structural analysis of oligomer and other assembly structures of lysozyme obtained from hen egg white and provided a quantitative estimation of a protein secondary structure in different states of its fibrillation. A strong amide I Raman band at 1660 cm-1 and a N-Cα-C stretching band at ∼930 cm-1 clearly indicated the presence of a substantial amount of α-helical folds of the protein in its oligomeric assembly state. In addition, analysis of the amide III region and Raman difference spectra suggested an ample presence of a PPII-like secondary structure in these oligomers without causing major loss of α-helical folds, which is found in the case of monomeric samples. Circular dichroism study also revealed the presence of typical α-helical folds in the oligomeric state. Nonetheless, most of the Raman bands associated with aromatic residues and disulfide (-S-S-) linkages broadened in the oligomeric state and indicated a collapse in the tertiary structure. In the fibrillar state of assembly, the amide I band became much sharper and enriched with the ß-sheet secondary structure. Also, the disulfide bond vibration in matured fibrils became much weaker compared to monomer and oligomers and thus confirmed certain loss/cleavage of this bond during fibrillation. The Raman band of tryptophan and tyrosine residues indicated that some of these residues experienced a greater hydrophobic microenvironment in the fibrillar state than the protein in the oligomeric state of the assembly structure.

Catalyst-Free and Rapid Chemical Approach for in Situ Growth of "Chemically Reactive" and Porous Polymeric Coating.

Design of "chemically reactive" coating with a tailored topography is a simple basis for optimizing various physical and chemical parameters, which is essential for achieving different biomimicked liquid wettability. In general, the essential topography and appropriate chemistry in the superhydrophobic coating is optimized following various top-down and bottom-up approaches, where various hydrophilic building blocks are associated using electrostatic interaction, hydrogen bonding, and other weak bonding (e.g., metal-thiol etc.), for both developing the desired hierarchical features and optimizing the appropriate chemistry on top of this featured interface. Such designs are inappropriate to sustain practically relentlessly harsh settings. So, further development for the synthesis of a durable and substrate-independent superhydrophobic coating is essential for various prospective applications in "real-world" scenarios. However, the design of highly abrasion-tolerant and "absolutely" substrate-independent artificial superhydrophobicity following a simple and scalable synthesis procedure is rare in literature. In this current work, a catalyst-free and facile chemical approach is adopted for an in situ and rapid deposition of a "chemically reactive" nanocomplex for decorating a wide range of substrates, including water-soluble, water-sensitive, highly flexible, rigid, and fibrous substrates with a highly tolerant biomimicked superhydrophobicity property. Branched poly(ethylenimine) (BPEI) and dipentaerythritol pentaacrylate (5Acl) mutually react through 1,4-conjugate addition reaction, and a hierarchically featured "chemically reactive" dip-coating is synthesized by the appropriate selection of the alcoholic solvent that is 1-heptanol. Furthermore, the choice of small alkylamines for post-covalent modifications of the "chemically reactive" dip-coating provided superhydrophobicity with a tailored water adhesion. A gradual increase in both roll-off angles, and the contact angle hysteresis (from 5° to 30°) was noted with a decrease in the hydrocarbon tail of selected alkylamines. The synthesized biomimicked interfaces are capable of performing under various practically relevant, severe physical and chemical challenges including bending, creasing, twisting, different physical abrasions (i.e., adhesive tape peeling test, abrasive sand paper test, etc.), high compressive strain, highly acidic and alkaline aqueous phases, artificial sea water, river water, etc. Moreover, this current approach was extended in developing various relevant functional materials, including superhydrophilic/superhydrophobic physical patterns on flexible papers and highly compressible super-oil-absorbent, etc.

Orientation of tyrosine side chain in neurotoxic Aß differs in two different secondary structures of the peptide.

Amyloid ß (Aß) peptide is present as a major component in amyloid plaque that is one of the hallmarks of Alzheimer's disease. The peptide contains a single tyrosine residue and Aß has a major implication in the pathology of the disease progression. Current investigation revealed that the tyrosine side chain attained two different critical stereo orientations in two dissimilar conformational states of the peptide. The extended α-helical structure of the peptide observed in an apolar solvent or methanol/water mixture became disordered in aqueous medium and the radius of gyration decreased. In aqueous medium, the torsional angle around Cα-Cß of tyrosine group became -60°. However, in its α-helical conformation in an apolar system, the measured angle was 180° and this rotameric state may be reasoned behind stronger tyrosine fluorescence compared with the disordered state of the peptide. Molecular dynamics simulation analyses and spectroscopic studies have helped us to understand the major structural changes in the secondary structure of the peptide in the two conformational states. A conformational clustering indicated that the compact state is more stable with tyrosine residue attaining the torsion angle value of -60°, whereas the native state (in HFIP/water mixture) is prevalent at a torsion angle value of -180°. High solvent accessibility has possibly stabilized the particular rotameric state (-60°) of the tyrosine residue and could be the reason behind decrease in fluorescence of the sole tyrosine residue in an aqueous buffer solution (pH 7.4) compared with its fluorescence in the α-helical structure in the micellar environment.

Synthesis and biological evaluation of a novel betulinic acid derivative as an inducer of apoptosis in human colon carcinoma cells (HT-29).

A novel family of betulinic acid analogues, carrying a triazole unit at C-3 attached through a linker, was synthesized by the application of azide-alkyne "Click reaction". These were screened for their anticancer activity against different cancer cells and normal human PBMC by MTT assay. Compound 2c [(3S)-3-{2-(4-(hydroxymethyl-1H-1,2,3-triazol-1-yl)acetyloxy}-lup-20(29)-en-28-oic acid] was found as the most potent inhibitor of cell line HT-29 with IC50 value 14.9 µM. Its role as an inducer of apoptosis was investigated in this cell line by Annexin-V/PI binding assay and by following its capability for ROS generation, depolarization of mitochondrial transmembrane potential, activation of caspases, PARP cleavage, nuclear degradation and expression of pro- and anti-apoptotic proteins. It exhibited much higher cytotoxicity than the standard drug 5-fluorouracil but showed negligible cytotoxicity towards normal PBMC. Elevated level of ROS generation, activation of caspase 3 and caspase 9, DNA fragmentation, higher expression of Bax and Bad, lower expression of Bcl2 and Bcl-xl, and increased level of Bax/Bcl-xl ratio identified 2c as a promising inducer of apoptosis that follows a mitochondria dependent pathway. Bio-physical studies indicate that compound 2c acts as a minor groove binder to the DNA.

Sequence complexity of amyloidogenic regions in intrinsically disordered human proteins.

An amyloidogenic region (AR) in a protein sequence plays a significant role in protein aggregation and amyloid formation. We have investigated the sequence complexity of AR that is present in intrinsically disordered human proteins. More than 80% human proteins in the disordered protein databases (DisProt+IDEAL) contained one or more ARs. With decrease of protein disorder, AR content in the protein sequence was decreased. A probability density distribution analysis and discrete analysis of AR sequences showed that ∼8% residue in a protein sequence was in AR and the region was in average 8 residues long. The residues in the AR were high in sequence complexity and it seldom overlapped with low complexity regions (LCR), which was largely abundant in disorder proteins. The sequences in the AR showed mixed conformational adaptability towards α-helix, ß-sheet/strand and coil conformations.

Synthesis and biological evaluation of andrographolide analogues as anti-cancer agents.

A new family of andrographolide analogues were synthesized and screened in vitro against kidney (HEK-293) and breast (MCF-7) cancer cells. The anti-cancer effects of the active analogues (2b, 2c and 4c) were determined by multiple cell based assays such as MTT, immunostaining, FACS, western blotting and transcriptional inhibition of NF-κB activity. Importantly, these compounds were found to possess higher anti-cancer potency than andrographolide and low toxicity to normal (VERO and MCF-10A) cells. Increased level of Bax/Bcl-xL ratio, caspase 3, and sub G1 population, higher expression level of tumor suppressor protein p53 and lower expression level of NF-κB suggested potent apoptotic property of the active analogues. Data revealed that the andrographolide derivative-mediated cell death in cancer cells was p53 dependent.