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Norcryptotackieine or 6H-indolo[2,3

OBJECTIVE: To determine the impact of the buccal envelope flap and pedicle design on the post-operative outcome and quality of life following lower third molar surgery (QoL). MATERIALS AND METHODS: A randomized case-control clinical study was carried out from September 2017 to September 2019. In this study, a total number of 50 patients with mandibular third molar impaction underwent surgical removal of the same using buccal envelope flap (group A) and pedicle flap (group B). The patients were assessed postoperatively for pain, swelling, trismus, wound dehiscence, dry socket, and quality of life for one month. RESULTS: In terms of pain, swelling, and trismus, there was no statistical difference between the two groups (p > 0.05). However, there was a statistically significant difference found in group B (pedicle flap) in terms of wound dehiscence, dry socket, and quality of life (p

Background/Purpose This research aimed to compare the effects of systemically prescribed Lycopene as a monotherapy and as an alternative to scaling and root planing in patients with chronic gingivitis. Materials and methods The participants were randomly assigned to one of two treatment groups: the experimental group (n = 50), which received 10 mg of Lycopene a day for two weeks, or the control group (n = 50) received a placebo for two weeks. For each category, quadrant distribution was randomized, with two quadrants receiving oral prophylaxis (OP) and two quadrants receiving no care (non-OP). At baseline, 1st, and 2nd weeks, the sulcus bleeding index, plaque index, gingival index, and salivary uric acid level were measured. Results All clinical criteria, including SBI, PI, GI, and salivary uric acid levels, showed a statistically significant decline in all patient types. Both clinical parameters were significantly reduced (p

Objectives: Attaining tumour material from lung cancer patients can be challenging with limited sample availability. Therefore, non-invasive means of assessing tumour material is becoming increasingly more important. Circulating tumour DNA (ctDNA), extracted from a blood sample is appealing for the patient, and can be performed serially over the course of treatment. Materials and Methods: Here, we describe an approach for profiling the blood samples of 103 NSCLC patients for 73 variants in ctDNA across a panel of actionable lung cancer mutations using the UltraSEEK lung Panel (Agena Biosciences). Results: Our cross-sectional study showed tumour and blood concordance in the detection of KRAS mutations (G12C, G12D, G12A/V, G12R, G12RC, Q61H) in 17/27 (63%), EGFR mutations (e746_a750del, e747_A750, T790M, L861Q) in 16/20 (80%) with additional PIK3CA_p545K mutations across both cohorts. In patients without reported tumour mutations, 11/56 (19.6%) presented with plasma mutations across EGFR, KRAS and PIK3CA. Where ctDNA mutations were measured longitudinally (n = 4 patients), the individual mutations mirrored the response to therapy/progression of disease. Conclusion: Whilst preliminary, this study demonstrates the utility of detecting clinically actionable mutations in the blood samples of NSCLC patients at the time of presentation, and over the course of therapy.

Single-component purely organic molecular crystals exhibiting negative thermal expansion (NTE) are extremely rare. Systematic studies on bromophenyl-substituted dihydro-imidazole, a novel single-co...

Transfer RNAs (tRNAs) are fundamental molecules in cellular translation. In this study we have highlighted a fluorescence-based perceptive approach for tRNAs by using a quinoxaline small molecule. We have synthesised a water-soluble fluorescent pyrimido-quinoxaline-fused heterocycle containing a mandatory piperazine tail (DS1) with a large Stokes shift (∼160 nm). The interaction between DS1 and tRNA results in significant fluorescence enhancement of the molecule with Kd ∼5 μM and multiple binding sites. Our work reveals that the DS1 binding site overlaps with the specific Mg2+ ion binding site in the D loop of tRNA. As a proof-of-concept, the molecule inhibited Pb2+ -induced cleavage of yeast tRNAPhe in the D loop. In competitive binding assays, the fluorescence of DS1-tRNA complex is quenched by a known tRNA-binder, tobramycin. This indicates the displacement of DS1 and, indeed, a substantiation of specific binding at the site of tertiary interaction in the central region of tRNA. The ability of compound DS1 to bind tRNA with a higher affinity compared to DNA and single-stranded RNA offers a promising approach to developing tRNA-based biomarker diagnostics in the future.

Targeted intracellular delivery is an efficient strategy for developing therapeutics against cancer and other intracellular infections. Nonspecific drug delivery shows limited clinical applications owing to high dosage, cytotoxicity, nonspecific action, high cost, etc. Therefore, targeted delivery of less cytotoxic drug candidates to hepatocytes through ASGPR-mediated endocytosis could be an efficient strategy to surmount the prevailing shortcomings. In the present work, the gene encoding ASGPR-H1-CRD was amplified from Huh7 cells, cloned into pET 11a vector, and the ASGPR-H1-CRD protein was expressed and purified from E. coli. A novel triantennary galactose-conjugated quinoline derivative 4 was synthesized that demonstrates 17-fold higher binding affinity to isolated ASGPR-H1-CRD protein receptor (Kd ∼54 μM) in comparison to D-galactose (Kd ∼900 μM). Moreover, micro-calorimetric studies for the interaction of glycoconjugate 4 with ASGPR protein on live hepatocytes showed notable thermal response in case of ASGPR-containing Huh7 cells, in comparison to non-ASGPR Chang cells. These results might serve as an approach towards targeted delivery of small glycoconjugates to hepatocytes.

RNA-biased small molecules with a monoquinoxaline core target the L-shaped structure of subdomain IIa of Hepatitis C virus internal ribosome entry site (IRES) RNA in proximity to the Mg2+ binding site. The binding event leads to the destacking of RNA bases, resulting in the inhibition of IRES-mediated translation and HCV RNA replication.

Presence of cyclobutane rings in bioactive natural products makes them a popular synthetic target. Most common strategy for synthesizing cyclobutanes is [2+2] cycloaddition, which is usually facilitated by using ultraviolet radiation and catalysts. Herein we report the design and synthesis of densely functionalized cyclobutanes by alleviating these drawbacks and using sunlight. Further, we identified the putative mechanism of the transformation based on kinetic, fluorescence and crystallographic studies and evaluated biological activities of the products against MCF7 cell lines. The rational design of the olefinic substrates was based on their UV–vis spectra. The generic aspect of the reaction was elucidated by the syntheses of diverse analogs of cyclobutanes. Further, crystal structures and UV–vis spectra of the olefinic partners assisted us in rationalizing the stereoselectivity of the heterodimers. We believe this energy-efficient mild approach will provide a substantial contribution to the existing repertoire of strategies to regio- and stereoselectively access cyclobutanes.

Cooperative disruption of Watson-Crick hydrogen bonds, as well as base-destacking, is shown to be triggered by a quinoxaline-based small molecule consisting of an N,N-dimethylaminopropyl tether, and a para-substituted benzyl moiety. This events lead to superstructure formation and DNA condensation as evident from biophysical experiments and classical molecular dynamics simulations. The DNA superstructure formation by mono-quinoxaline derivatives is highly entropically favored and predominantly driven by hydrophobic interactions. Furthermore, oversupercoiling of DNA and base-destacking cumulatively induces histone eviction from in-vitro assembled nucleosomes at lower micromolar concentrations implicating biological relevance. The DNA structural modulation and histone eviction capacity of the benzyl para-substituents are in the order: –I > –CF3> -Br > -Me > -OMe > –OH, which is largely guided by the polarity of benzyl para-substituent and the resulting molecular topology. The most hydrophobic derivative 3c with para-iodo benzyl moiety causes maximal disruption of base pairing and generation of superstructures. Both these events gradually diminish as the polarity of the benzyl para-substituent increases. On the other hand, quinoxaline derivatives having heterocyclic ring instead of benzyl ring, or in the absence of N,N-dimethylamino head-group, is incapable of inducing any DNA structural change and histone eviction. Further, the quinoxaline compounds displayed potent anticancer activities against different cancer cell lines which directly correlates with the hydrophobic effects of the benzyl para-substituents. Overall, the present study provides new insights into the mechanistic approach of DNA structural modulation driven histone eviction guided by the hydrophobicity of synthesized compounds leading to cellular cytotoxicity towards cancer cells.

Reactive Oxygen Species (ROS) results from oxidative stress due to the improper balance between ROS and antioxidant is an important factor in the pathogenesis of various diseases, such as cardiovascular disorders, neurological conditions, Parkinson’s disease, rheumatoid arthritis, and ageing..

Small molecules that intercalate DNA have tremendous therapeutic potential. Typically, DNA intercalators do not alter the overall DNA double-helical structure, except locally at the intercalation sites. In a previous report, we showed that a quinoxaline-based intercalator with a mandatory benzyl substitution (1d) induced an unusually large circular dichroism signal upon DNA binding, suggesting the formation of intercalated DNA superstructures. However, no detailed structural studies have been reported. Using atomic force microscopy, we have probed the nature of the superstructure and report the formation of a plectonemically oversupercoiled structure of pBR322 plasmid DNA by 1d, where close association of distant DNA double-helical stretches is the predominant motif. Without the benzyl moiety (1a), no such DNA superstructure was observed. Similar superstructures were also observed with doxorubicin (dox), a therapeutically important DNA intercalator, suggesting that the superstructure is common to some intercalators. The superstructure formation, for both intercalators, was observed to be GC-specific. Interestingly, at higher concentrations (1d and dox), the DNA superstructure led to DNA condensation, a phenomenon typically associated with polyamines but not intercalators. The superstructure may have important biological relevance in connection to a recent study in which dox was shown to evict histone at micromolar concentrations.

Nonalcoholic fatty liver disease (NAFLD), which is characterized by excess accumulation of triglyceride in hepatocytes, is the major cause of chronic liver disease worldwide and no approved drug is available. The mechanistic target of rapamycin (mTOR) complexes has been implicated in promoting lipogenesis and fat accumulation in the liver, and thus, serve as attractive drug targets. The generation of non- or low cytotoxic mTOR inhibitors is required because existing cytotoxic mTOR inhibitors are not useful for NAFLD therapy. New compounds based on the privileged adenosine triphosphate (ATP) site binder quinoline scaffold conjugated to glucose and galactosamine derivatives, which have significantly low cytotoxicity, but strong mTORC1 inhibitory activity at low micromolar concentrations, have been synthesized. These compounds also effectively inhibit the rate of lipogenesis and lipid accumulation in cultured hepatocytes. This is the first report of glycomimetic-quinoline derivatives that reduce lipid load in hepatocytes.

This paper is concerned with portfolio selection problem using a fuzzy stochastic price scenario. In this scenario, a ratio factor (k) is calculated from the historical data to generated the future price of the stocks of Bombay Stock Exchange. The ratio factor k of different stocks are treated as a fuzzy numbers, which in turn gives future fuzzy prices of the stocks. Returns on the stocks are calculated from the future price of the stocks. Rejection of the assets are done based on returns calculated from the worst case scenario. If the returns of an asset exceed the investor's risk tolerance then the asset are not included in the portfolio. The definition of capital budget has been reformed to include the transaction cost with the capital budget. This process is implemented in two stage multi-objective fuzzy probabilistic programming problem which is then solved using a fuzzy genetic algorithm to obtain maximum short term and long term returns. A case study of Bombay Stock Exchange is provided to illustrate the above model.

Reversibility between two concomitant polymorphs and their switching ability is demonstrated for the novel organic nonlinear optical (NLO) material Z-3-(3-methoxyphynyl)-2-(4-nitrophenyl)acrylonitrile. The appearances of their concomitant as well as exclusive polymorphic forms were discovered upon systematic crystallization experiments using various solvents. Determination of X-ray crystal structures confirmed that the polymorphs crystallize in centrosymmetric (P21/n) and non-centrosymmetric (Fdd2) space groups. A search using the Cambridge Structural Database revealed that there exist only 10 such polymorphic pairs. Reversible phase transitions and the switching ability between the polymorphs can be achieved via both heat and solvents as stimuli. Structural analysis confirmed that the polymorphs have two-dimensional similarity. Further, quantitative and qualitative analysis of interaction energies based on the UNI force field and energy frameworks indicate that they possess very similar energies, althoug...

An efficient solvent free Pd(pCH2S)2dba catalyzed green-chemical strategy for the synthesis of diaryl disulfides from aryl thiols in moderate to excellent yield is reported. Variety of diaryl disulfides were synthesized. The catalyst is recyclable up to four cycles.

Our attempts to cocrystallize three sulfa drugs (SDs), viz., sulfamerazine (smr), sulfamethazine (smz) and sulfamethoxazole (smx) with four coformers, viz., niflumic acid and flufenamic acid, 4-aminopyridine and piperazine led to eight new solids. Although the molecular structures of smr, smx and smz are comparable, their propensities to form multiple solid forms with the four selected coformers were found to be different. smr and smx reacted with 4-aminopyridine and piperazine yielding four salts while its reaction with niflumic and flufenamic acids resulted in the precipitation of only the reactants. In contrast, smz formed cocrystals with niflumic and flufenamic acids and salts with 4-aminopyridine and piperazine. To understand this discrepancy, we investigated the structural chemistry of these solids by analysing the interactions of key synthons present in the single component SDs as well as those reported in the literature. The study reveals that recognition of the nature of key synthons occurring in single component SDs and the ability to break and form new synthons with coformers can be a viable strategy to design multicomponent solids based on sulfa drugs.

Structural integrity of the bacterial genome plays an important role in bacterial survival. Cellular consequences of an intolerable amount of change in the DNA structure are not well understood in bacteria. Here we have stated that binding of synthetic 6-nitroquinoxaline derivatives with DNA led to change in its global structure, subsequently culminating with over-supercoiled form through in-path intermediates. This structural change results in induction of programmed cell death like physiological hallmarks, which is dependent on substitution driven structural modulation properties of the scaffold. A sublethal dose of a representative derivative

Traditionally, lead and heavy metal containing inorganic oxides dominate the area of ferroelectricity. Although, recently, lightweight non-toxic organic ferroelectrics have emerged as excellent alternatives, achieving higher temperature up to which the ferroelectric phase can persist has remained a challenge. Moreover, only a few of those are single-component molecular ferroelectrics and were discovered upon revisiting their crystal structures. Here we report a novel phenanthroimidazole derivative, which not only displays notable spontaneous and highly stable remnant polarizations with a low coercive field but also retains its ferroelectric phase up to a record-high temperature of ∼521 K. Subsequently, the crystal undergoes phase transition to form non-polar and centrosymmetric polymorphs, the first study of its kind in a single-component ferroelectric crystal. Moreover, the compound exhibits a significantly high thermal stability. Given the excellent figures-of-merit for ferroelectricity, this material is likely to find potential applications in microelectronic devices pertaining to non-volatile memory.

Natural anthraquinone compounds have emerged as potent anticancer chemotherapeutic agents because of their promising DNA-binding properties. Aloe vera is among one of the very well-known medicinal plants, and the anthraquinone derivatives like aloe emodin (ALM), aloins (ALN), and aloe emodin-8-glucoside (ALMG) are known to have immense biological activities. Here, we have used biophysical methods to elucidate the comparative DNA-binding abilities of these three molecules. Steady-state fluorescence study indicated complexation between calf thymus DNA (ctDNA) and both the molecules ALM and ALMG whereas ALN showed very weak interaction with DNA. Displacement assays with ctDNA-bound intercalator (ethidium bromide) and a groove binder (Hoechst 33258) indicated preferential binding of both ALM and ALMG to minor groove of DNA. Isothermal titration calorimetric (ITC) data suggested spontaneous exothermic single binding mode of both the molecules: ALM and ALMG. Entropy is the most important factor which contributed to the standard molar Gibbs energy associated with relatively small favorable enthalpic contribution. The equilibrium constants of binding to ctDNA were (6.02 ± 0.10) × 104 M-1 and (4.90 ± 0.11) × 104 M-1 at 298.15 K, for ALM and ALMG, respectively. The enthalpy vs temperature plot yielded negative standard molar heat capacity value, and a strong negative correlation between enthalpy and entropy terms was observed which indicates the enthalpy entropy compensation behavior in both systems. All these thermodynamic phenomena indicate that hydrophobic force is the key factor which is involved in the binding process. Moreover, the enhancement of thermal stability of DNA helix by ALM and ALMG fully agreed to the complexation of these molecules with DNA.

This paper is concerned with multi-objective fuzzy stochastic model for determination of optimum cropping patterns with water balance for the next crop season. The objective functions of the model is to study the effect of various cropping patterns on crop production subject to total water supply in a small farm. The decision variables are the cultivated area of different crops at the farm. The water requirement of the crops follows fuzzy uniform distribution and yields in the objective functions are taken as a fuzzy numbers. The model is solved by using fuzzy stochastic simulation based genetic algorithm without deriving the deterministic equivalents.

This paper is concerned with the solution procedure of a multi-objective transportation problem with fuzzy stochastic simulation based genetic algorithm. Supplies and demands are considered as a fuzzy random variables with fuzzy means and fuzzy variances in proposed multi-objective fuzzy stochastic transportation problem. The first step in fuzzy simulation based genetic algorithm is to deal with aspiration level of the constraints with the help of alpha-cut technique to obtain multi-objective stochastic transportation problem. In next step, fuzzy probabilistic constraints (fuzzy chance constraints) are handled within fuzzy stochastic simulation based genetic algorithm to obtain a feasible region. The feasibilities of the chance constraints are checked by the stochastic programming with the genetic process without deriving the deterministic equivalents. The feasibility condition for the transportation problem is maintained through out the problem. Finally, multiple objective functions are considered in order to generate a Pareto optimal solutions for the fuzzy stochastic transportation problem using the proposed algorithm. The proposed procedure is illustrated by two numerical examples.

Three isostructural polymorphs with two-dimensional and three-dimensional similarities are demonstrated quantitatively from similarity relationship analysis. The similarity dimensions are then visualized and correlated in a novel way via qualitative analysis using ‘energy frameworks’. Two of the three polymorphs with three-dimensional similarities exhibiting identical physical properties have almost equi-energetic crystal structures while the most stable third polymorph exhibits distinct properties. Thereby, structure–property correlations are derived, both quantitatively and qualitatively.

The effect of the non-ionic surfactant Tween 40 (TW40) on Human Serum Albumin (HSA) has been studied by spectroscopic and isothermal titration calorimetric (ITC) methods. Our steady-state and time-resolved spectroscopic results reveal the perturbation of the native protein conformation upon interaction with TW40. The interaction of TW40 with HSA does not occur in a sequential manner unlike another anionic surfactant, sodium dodecyl sulfate (SDS). Our major conclusion is that the HSA–TW40 interaction is mainly driven by weak forces like van der Waal/hydrogen bonding interactions. This is also generalized from the results of interaction of HSA with another non-ionic surfactant TW80.

Background: Due to competitiveness and academic benefits, most dental professionals feel an urgent need to increase their publications. Hence, we explored the attitude of students and faculty members toward scientific publications through a questionnaire. Materials and Methods: A questionnaire consisting of 13 questions was sent by e-mails and posting the printed copies to dental postgraduate (PG) students (second and third year) and faculty members ( n = 500 each). The returned completed questionnaires were analyzed. Results: About 37% of dental PG faculty and 35.6% PG students responded to the questionnaire, with overall response of 72.6%. Among the PG faculty, professors (P) had more scientific publications, followed by senior lecturers (SL) and readers (R). The publications as first or corresponding author were less among both faculty and PG students while co-authorship was more among PG students compared to faculty members. Awareness about the term plagiarism was overall high and relatively highest among R, followed by SL, P and PG students. The percentage of publications in fee charging journals was more among PG students than faculty members and self-funding for publication was observed in 86.4% of PG students and 94-100% among faculty members. Conclusion: About 72.6% of dental professionals were involved in publishing of their research work and the number of publications increased steadily with an increase in their academic experience. All the dental professionals concurred publications as the criteria for academic excellence.

We have developed a novel fluorescent scaffold 4 which is a 9-nitro-2,3-dihydro-1H-pyrimido[1,2-a]quinoxalin-5-amine derivative from the reaction between di-tert-butyl but-2-ynedioate and a quinoxaline molecule containing a dimethyl amine side tail in high yield. The synthesis of scaffold 4 involves an sp3 C–N bond cleavage mechanism which is not very common. The scaffolds 4 is emissive in the visible range λem ∼ (517–540) nm with large stokes shifts (5005–6378) cm−1 in ethanol. Laser confocal microscopy of the live HepG2 cells treated with compound 4f shows that it can be used for live cell imaging in nanomolar concentrations.