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In the present study, we have synthesized a series of novel 2-(3-substituted-4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydrophthalazine-1,4-diones by the reaction of 3-(substituted)-2-hydrazino-quinazoline-4(3H)-ones with phthalic anhydride. The starting material 3-(substituted)-2-hydrazino-quinazolin-4(3H)-ones were synthesized from various primary amines. All the synthesized compounds were screened for their antitubercular, anti-HIV and antibacterial activity against different gram positive and gram negative strains by agar dilution method. Among the test compounds, 2-(3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)-2,3-dihydrophthalazine-1,4-dione (QCT7) shown most potent antibacterial activity against E. coli, and S. aureus with the MIC of 3 µg/mL. The compound QCT7 exhibited the antitubercular activity with the MIC of 25 µg/mL and anti-HIV activity with the EC50 of 43.68 µM against HIV1 and HIV2 and offers potential lead for further optimization and development to new antitubercular and anti-HIV agents. The results obtained from this study confirm that the synthesized and biologically evaluated quinazolines showed promising antimicrobial, antitubercular and anti-HIV activities and are new scaffolds for antimicrobial activity.

Duplicate and Accumulate (MAC) is one of the central practices utilized absolutely in signal- controlling and different applications. The multiplier is the major piece of Digital Signal Processors (DSPs). Its cutoff spins around power, LUT use, and surrender pick the presence of a DSP. In like way, there is a need to sort out the drive and give up fit multiplier. In this paper, a 16-digit MAC unit is proposed to utilize an 8-cycle Vedic multiplier and pass on a save snake. A relationship with the current 8-cycle Vedic multiplier utilizing Square-Root (SQR) Carry-select snake (CSLA) is introduced. It is isolated and a standard pack multiplier. The whole technique is done in Verilog HDL. Blend and redirections were finished utilizing Xilinx InDesign Suite 14.5. The proposed game plan accomplishes fundamental improvement in region and suspension. In like manner, an abatement in power around 9.5% is refined.

Background: With the goal of developing Alzheimer's disease therapeutics, we have designed and synthesized novel piperidone fused dipeptide (DPPS) derivatives possessing dual action such as acetylcholinesterase (AChE) and beta-amyloid peptide (Aβ) aggregation inhibition. Designed peptide was synthesized by solid phase peptide synthesis using FMOC chemistry protocol and characterized by mass spectroscopy. Methods: The amino acid sequence in peptide was analyzed by LC-MS-MS. In silico docking analysis was carried out using GLIDE software. The docking score using GLIDE was found to be -7.88 against AChE and -9.74 against BACE1 enzyme. In vitro enzyme inhibition assay was carried out for AChE enzyme and BACE1 enzyme. Results: The IC50 values of AChE inhibition and BACE1 of DPPS were found to be 0.4796 μM/ml and 0.0154 μM/ml, respectively. The correlation of in silico and in vitro results showed that DPPS possessed a greater ability to inhibit BACE1 enzyme.

Introduction: A biologically active benzimidazole synthesis was carried out at laboratory scale in order to reduce environmental pollution as well as to identify effective synthetic route. Methods: In this connection optimization was performed by Central Composite Rotatable Design (CCRD) to develop experimental data through Response Surface Methodology (RSM). The optimization of title analogue was performed by RSM which led us to the identification of high quality of synthetic yield. The effects of four independent parameters [1-5 mol of oxobutanoic acid (X1), 1-5 mol of thionyl chloride (X2), 1-5 mol of imidazol-2-yl-4-oxobutanoyl chloride (X3), and 1-5 mol of 4-nitro aniline (X4) were taken into optimize the synthetic yields of title scaffold. Results and Conclusion: A result of randomly generated benchmark and real values such as percentage yield, λmax and Retention Time (RT) of title compound are found to be highly significant. The present model is connected to maximize the percentage yield of title scaffold with the developed optimal set. The highly significant benzimidazole was screened for its MTB activity against MTB H37Ra strain by MABA screening.

The present treatments for HIV transfection include chemical agents and gene therapies. Although many chemical drugs, peptides and genes have been developed for HIV inhibition, a variety of non-ignorable drawbacks limited the efficiency of these materials. Dendrimers has ability to carrier of antiviral drugs due to some properties such as mono-dispersity, defined structure, amenability for functionalization using diverse ligands and its low-nanometer size. In this review, we discuss the application of dendrimers as both therapeutic agents and non-viral vectors of chemical agents and genes for HIV treatment. In one way, dendrimers with functional end groups combine with the gp120 of HIV and CD4 molecule of host cell to suppress the attachment of HIV to the host cell. In another way, dendrimers are also able to transfer chemical drugs and genes into the host cells, which increase the anti-HIV activity of these materials. Dendrimers as therapeutic tools provide a potential treatment for HIV infection. Keywords: Dendrimers, Drug release, Drug targeting, gp120, CD4, Antiviral drug

Hit, Lead & Candidate Discovery A variety of novel 2-(methyl/phenyl)-3-(4-(5-substituted-1,3,4-oxadiazol-2-yl)phenyl) quinazolin-4(3H)-ones have been synthesized by treating 3-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl)-2-(methyl/phenyl)-quinazolin-4(3H)-one with a variety of secondary amines. Graph theoretical analysis was used in identification of drug target that is, NMDAR (N-methyl-d-aspartate receptors). The observed reports of in silico modeling and ligand based toxicity, metabolism prediction studies were encouraging us to synthesize of title compounds and evaluate their antiepileptic effects. The title compounds were tested for its antiepileptic potency by MES and scPTZ model. Rotorod test is used to assess its neurotoxicity. In the preliminary test it was found that in MES test, analogs 6d, 6e, 6f, and 6l were potent; whereas in scPTZ test analogs 6d, 6e, 6f, and 6k displayed potent antiepileptic activity. Additionally these five derivatives were tested in rats orally at a dose of 30 mg/kg and found that compounds 2-methyl-3-(4-(5-morpholino-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4(3H)-one 6e and 2-methyl-3-(4-(5-(piperidin-1-yl)-1,3,4-oxadiazol-2-yl)phenyl)quinazolin-4(3H)-one 6f exhibited superior activity than reference Phenytoin. In MES test, these derivatives 6e and 6f showed activity at 30 mg/kg i.p. dose after 0.5 hr and 4.0 hr. In scPTZ test these derivatives 6e and 6f showed activity at 100 and 300 mg/kg i.p. dose after 0.5 hr and 4.0 hr, respectively.

Hit, Lead & Candidate Discovery A series of 2-(2-substituted benzylidenehydrazinyl-2-oxopropyl)-3-(4-[4-oxo-2-phenylthiazolo din-3-yl]phenyl)quinazolin-4(3H)-one 7a-7l were synthesized and characterized by IR, 1 H-NMR, 13 C-NMR, mass spectroscopy and elemental analyses. In this present study, the density functionality theory was performed to identify drug stability. Further we introduced graph theoretical analysis by utilised Kyoto Encyclopedia of Genes and Genomes (KEGG) database and Cytoscape software to identify drug target. Based on the observed drug target insilico modeling was executed to know effective drug. The antiepileptic effects of title compounds were evaluated by using MES and subcutaneous pentylenetetrazole (scPTZ) test. Acute neurological toxicity of title compounds was studied by using standardized rotorod test. After 0.5 hr of period many of the compounds showed anticonvulsant activity at MES or scPTZ test. Comparison of the biological activity of test compounds with its chemical structures indicates that, compounds possessing electron donating group exhibited superior activity than the analogs having electron withdrawing moieties. Among the electron donating group tested, amino derivative exhibited good activity than rest of derivatives. From the study it was concluded that, the compound 7j was established as very potent compared with rest of the compounds and standard drugs subjected to biological studies. Thus the compound 2-(2-[4-aminobenzylidene]hydrazinyl-2-oxopropyl)-3-(4-[4-oxo-2-phenylthiazolidin-3-yl]phenyl) quinazolin-4(3H)-one (7j) came out as pilot derivative without any neurotoxicity with a wide spectrum of antiepileptic activity. HIGHLIGHTS: The performed work is having great significance in terms of Graph theoretical analysis used to identify drug target In silico modeling used to identify designed drug interaction with identify target Density functionality studies used to identify synthesized compound energy band gap which is correlate with enhancement of its biological activity Antiepileptic effects of entire synthesized quinazolinone scaffolds were evaluated by MES and scPTZ test 2-(2-[4-aminobenzylidene]hydrazinyl-2-oxopropyl)-3-(4-[4-oxo-2-phenylthiazolidin-3-yl]phenyl) quinazolin-4(3H)-one (7j) was established as very potent compared to the rest of the compounds and standard drugs which were subjected to biological studies.

The combination of natural and synthetic polymeric materials grafted hydrogels offer great potential as oral therapeutic systems because of its intrinsic biocompatibility, biodegradability, protect labile drugs from metabolism and controlled release properties. Hence, in the present study, we aimed to prepare and optimize oral delivered pH-responsive Zein-co-acrylic acid hydrogels incorporated with 5-fluorouracil (5-Fu) and rutin (Ru) for effective anticancer activity with less toxicity. In this study, graft polymerization technique is adopted to formulate hydrogels with various ratios of Zein, acrylic acid, N, N-methylene bisacrylamide, and ammonium persulphate as an initiator. The optimized formulation was identified based on the cross-linking, chemical interactions, intrinsic viscosity (η), dynamic swelling (Q) at pH 1.2, diffusion coefficient (D), sol–gel fraction (%), and porosity (%). The selected optimized formulation has shown significant improvement in drugs loading and encapsulation efficiency, releasing at pH 1.2 and pH 7.4. Drug release kinetics studies confirmed the controlled release properties of hydrogels. Hydrogels were porous and the drug loading of 5-Fu and Ru was found to be 12.13% and 10.86%, respectively, whereas encapsulation efficiency of 5-Fu and Ru was 89.35% and 81.47%, respectively. Furthermore, form the in vitro cytotoxic screening, it was found that 52.5 µg mL−1 5-Fu and Ru-loaded hydrogel impacted 50% of cell death at 24 h, there by significantly arresting the proliferation of MDA-MB-231 and MCF-7 breast cancer cell lines. Altogether, the optimized pH-responsive hydrogels make them favorable carrier for anticancer drugs for oral delivery.

The combination of natural and synthetic polymeric materials grafted hydrogels offer great potential as oral therapeutic systems because of its intrinsic biocompatibility, biodegradability, protect labile drugs from metabolism and controlled release properties. Hence, in the present study, we aimed to prepare and optimize oral delivered pH-responsive Zein-co-acrylic acid hydrogels incorporated with 5-fluorouracil (5-Fu) and rutin (Ru) for effective anticancer activity with less toxicity. In this study, graft polymerization technique is adopted to formulate hydrogels with various ratios of Zein, acrylic acid, N, N-methylene bisacrylamide, and ammonium persulphate as an initiator. The optimized formulation was identified based on the cross-linking, chemical interactions, intrinsic viscosity (η), dynamic swelling (Q) at pH 1.2, diffusion coefficient (D), sol–gel fraction (%), and porosity (%). The selected optimized formulation has shown significant improvement in drugs loading and encapsulation efficiency, releasing at pH 1.2 and pH 7.4. Drug release kinetics studies confirmed the controlled release properties of hydrogels. Hydrogels were porous and the drug loading of 5-Fu and Ru was found to be 12.13% and 10.86%, respectively, whereas encapsulation efficiency of 5-Fu and Ru was 89.35% and 81.47%, respectively. Furthermore, form the in vitro cytotoxic screening, it was found that 52.5 µg mL(−1) 5-Fu and Ru-loaded hydrogel impacted 50% of cell death at 24 h, there by significantly arresting the proliferation of MDA-MB-231 and MCF-7 breast cancer cell lines. Altogether, the optimized pH-responsive hydrogels make them favorable carrier for anticancer drugs for oral delivery.

A series of 1-(substitutedbenzylidene)-4-(4-(2-(methyl/phenyl)-4-oxoquinazolin-3(4 H )-yl) phenyl)semicarbazide derivatives were synthesized with the aim of developing potential antimicrobials. It was characterized by FT-IR, 1 H NMR, Mass spectroscopy and elemental analysis. In addition, the in vitro antibacterial and antifungal properties were tested against some human pathogenic microorganisms by employing the disc diffusion technique and agar streak dilution method. All title compounds showed activity against the entire strain of microorganisms. The relationship between the functional group variation and the biological activity of the evaluated compounds were well discussed. Based on the results obtained, compound 5j was found to be very active compared to the rest of the compounds which were subjected to antimicrobial assay.

Background We designed to synthesize a number of 2-(2-(substituted benzylidene) hydrazinyl)-N-(4-((3-(phenyl imino)-3,4-dihydro quinoxalin-2(1 H)-ylidene)amino) phenyl) acetamide S1-S13 with the hope to obtain more active and less toxic anti-microbial and anti-TB agents. Methods A series of novel quinoxaline Schiff bases S1-S13 were synthesized from o-phenylenediamine and oxalic acid by a multistep synthesis. In present work, we are introducing graph theoretical analysis to identify drug target. In the connection of graph theoretical analysis, we utilised KEGG database and Cytoscape software. All the title compounds were evaluated for their in-vitro anti-microbial activity by using agar well diffusion method at three different concentration levels (50, 100 and 150 µg/ml). The MIC of the compounds was also determined by agar streak dilution method. Results The identified study report through graph theoretical analysis were highlights that the key virulence factor for pathogenic mycobacteria is a eukaryotic-like serine/threonine protein kinase, termed PknG. All compounds were found to display significant activity against entire tested bacteria and fungi. In addition the synthesized scaffolds were screened for their in vitro antituberculosis (anti-TB) activity against Mycobacterium tuberculosis (Mtb) strain H37Ra using standard drug Rifampicin. Conclusion A number of analogs found markedly potent anti-microbial and anti-TB activity. The relationship between the functional group variation and the biological activity of the evaluated compounds were well discussed. The observed study report was showing that the compound S6 (4-nitro substitution) exhibited most potent effective anti-microbial and anti-TB activity out of various tested compounds.

Most of the drugs and pharmacologically relevant molecules possess heterocyclic ring structures and presence of hetero atoms or groupings divulges privileged specificities in their pharmacological targets. Especially the heterocyclic systems, quinazoline is a biologically imperative scaffold known to be linked with several pharmacological activities. Some of the protuberant pharmacological responses attributed to this system are analgesic, anti-inflammatory, anti-convulsant, sedative-hypnotic, anti-histaminic, anti-hypertensive, anti-cancer, anti-microbial, anti-tubercular and anti-viral activities. This multiplicity in the pharmacological response contours of quinazoline has attracted the consideration of medicinal chemists to explore this system to its multiple potential against numerous activities. Several of these synthetic and pharmacological investigations have been successively studied for structure-activity relationship (SAR) to correlate the particular structural features for their pharmacological target. The emerging understanding of quinazoline derivatives on their pharmacological target offer opportunities for novel therapeutics. This review principally emphases on the medicinal chemistry aspects including drug design, structure–activity relationships (SARs), and mechanism of actions of quinazoline derivatives. This review gives detailed attention on in vitro and in vivo pharmacological activities of quinazoline and its analogs in the perspective of drug discovery and its development.

A simple, rapid, selective, sensitive, linear, precise and accurate stability indicating RP-HPLC method was developed and validated for the simultaneous estimation of Atenolol and Nifedipine in pharmaceutical dosage form. Separation was attained on a STD Kromasil C18 (150 x 4.6 mm, 5 μ particle size) column at 30°C using a mobile phase consisting of phosphate buffer (pH 5.0) and acetonitrile in the ratio of 45: 55% v/v, at a flow rate of 1.0 ml/min. The UV detection wavelength was 232 nm and 10 μl of sample was injected. The linearity was found to be 15–90 μg/ml for Atenolol and 6–36 μg/ml for Nifedipine with a correlation coefficient of 0.9993 and 0.9994, respectively. Retention times were found to be 2.474 min and 4.553 min for Atenolol and Nifedipine, respectively. The overall mean % recoveries were found to be 99.69% for Atenolol and 99.68% for Nifedipine. The method was validated as per the ICH guidelines for sensitivity, linearity, accuracy and precision. The % RSD for precision, robustness and ruggedness of the proposed method was found to be less than 2%. Further forced degradation studies were conducted for indicating the stability of the method developed. Hence the developed method can be successfully employed for routine quality control analysis of Atenolol and Nifedipine in pharmaceutical dosage forms.

A simple and sensitive gradient RP-HPLC method was developed for the simultaneous estimation of Hydrochlorthiazide and Olmesartan medoxomil present in bulk and their pharmaceutical dosage form using Inertsil ODS C18 (150 × 4.6 mm i.d, packed with 5 μ particle size) column at 30°C in an gradient mode with mobile phase comprising 0.2% acetate buffer: Acetonitrile. The flow rate was 1.2 ml/min and effluent was monitored at 252 nm. The retention time were found to be 5.080 min for Hydrochlorthiazide and 10.493 min for Olmesartan, respectively. The assay exhibited a linear concentration range of 25–150 μg/ml for Hydrochlorthiazide and 20–120 μg/ml for Olmesartan with a correlation coefficient of 0.9998 for Hydrochlorthiazide and 0.9994 for Olmesartan, respectively. The overall mean % recovery was found to be 100.2 for Hydrochlorthiazide and 101.4 for Olmesartan, respectively. The proposed method was statistically developed and validated as per ICH guidelines and can be applied for routine quality control analysis of Hydrochlorthiazide and Olmesartan medoxomil in pharmaceutical dosage forms.

In the remote districts of the Dar Es Salaam periphery, low density and urban sprawl do not facilitate connection to basic urban infrastructures. Through the analysis of the district of Ilala, this article focuses on the modalities and effects of electrification of these areas located at the end of the network. Strongly supported by the inhabitants, TANESCO's access to electricity is finally made possible, thanks to the subsidized extension of its networks, thus quickly relegating the few off-grid backup electrical systems (generators, solar systems). But counter-intuitively, the arrival of electricity does not mean that other pre-existing energy sources (such as kerosene and coal) disappear. In these intermediate areas between the city and the countryside, there is rather an 'energy diversification', resulting from the widening of the available offers: users quickly adopt electricity to access new services more easily (television, refrigerator, light bulb) while continuing to prefer non-electric energy for other domestic uses (cooking and ironing with coal, for example; or occasional lighting and rapid cooking with kerosene). Less expensive, easily available, requiring minimal equipment, these so-called traditional energies will continue to be used alongside new exclusively electrical uses. This diversification is neglected in the country's energy strategy, which focuses on electricity despite the financial difficulties in implementing it. Documented in the literature, the explanatory factors of household fuel choices are usually centered on user practices, but more rarely placed in a broader perspective of understanding energy governance. By revealing the structural factors of energy diversification in intermediate spaces undergoing electrification, this article contributes to the reflections on the particularities of the energy transition in order to better understand the particularities of African urbanization., Dans les quartiers lointains de la périphérie de Dar Es Salaam, la faible densité et l’étalement urbain ne facilitent pas le raccordement aux infrastructures urbaines de base. A travers l’analyse du district d’Ilala, cet article s’intéresse aux modalités et aux effets de l’électrification de ces espaces situés en bout de réseau. Fortement plébiscité par les habitants, l’accès à l’électricité de la TANESCO est finalement permise grâce à l’extension subventionnée de ses réseaux, reléguant alors vite les quelques systèmes électriques d’appoint hors-réseau (groupes électrogènes, systèmes solaires). Mais de manière contre-intuitive, l’arrivée de l’électricité ne provoque pas pour autant la disparition des autres sources énergétiques lui préexistantes (comme le kérosène et le charbon). Dans ces zones intermédiaires entre la ville et la campagne, on observe plutôt une ‘diversification énergétique’, résultante de l’élargissement de l’offre disponible : les usagers adoptent rapidement l’électricité pour accéder plus aisément à de nouveaux services (télévision, frigidaire, éclairage à l’ampoule) tout en continuant à préférer des énergies non-électriques pour d’autres usages domestiques (cuisson et repassage au charbon par exemple ; ou éclairage ponctuel et cuisson rapide au kérosène). Moins chères, facilement disponible, nécessitant un équipement minimal, ces énergies dites traditionnelles sont amenés à perdurer dans les pratiques aux côtés de nouveaux usages exclusivement électriques. Cette diversification est négligée dans la stratégie énergétique du pays, centrée sur l’électricité malgré les difficultés financières à la mettre en place. Documentés par la littérature, les facteurs explicatifs des choix de combustibles des ménages sont habituellement centrés sur les pratiques des usagers, mais plus rarement replacés dans une perspective de compréhension plus large de gouvernance énergétique. En révélant les facteurs structurels de la diversification énergétique des espaces intermédiaires en cours d’électrification, cet article permet ainsi de contribuer aux réflexions sur les particularités de la transition énergétique pour in fine mieux appréhender les particularités de l’urbanisation africaine.

The Central Asian wolves form a cohort within the wolf-dog clade known as the wooly wolf (Canis lupus chanco). These wolves are poorly studied and their current extent and distribution remain unknown. Apex predators already existing at higher elevations like wooly wolves can be severely affected by climate change because of the absence of suitable refuge. Concomitantly, in the era of Anthropocene, the change in land use land cover (LULC) is rapidly increasing. Even the most adaptable species occurring in human-dominated landscapes may fail to survive under the combined impact of both climate change and human pressure. We collected 3,776 presence locations of the wooly wolf across its range from published literature and compiled 39 predictor variables for species distribution modeling, which included anthropogenic factors, climatic, vegetation, and topographic features. We predicted the change in their distribution under different anthropogenic factors, climate change, and land-use land-cover change scenarios. Wolf showed affinity toward areas with low to moderately warm temperatures and higher precipitations. It showed negative relationships with forests and farmlands. Our future projections showed an expansion of wolf distribution and habitat suitability under the combined effects of future climate and LULC change. Myanmar and Russia had the introduction of high and medium suitability areas for the wooly wolf in future scenarios. Uzbekistan and Kazakhstan showed the consistent loss in high suitability areas while Mongolia and Bhutan had the largest gain in high suitability areas. The study holds great significance for the protection and management of this species and also provides opportunities to explore the impact on associated species., This research was supported by the Wildlife Institute of India. We are thankful to the Director and Dean, Wildlife Institute of India, for support and encouragement. This work was carried out under the project “Response to Anthropocene and Climate Change: Movement Ecology of Selected Mammal Species in the Indian Himalayan region” funded by the National Mission on Himalayan Studies (NMHS).

In predominantly agrarian economies with limited irrigation, rainfall plays a critical role in shaping households’ incomes and subsequently their spending decisions. This study uses household-level panel data from a nationally representative survey in India to estimate the effect of agricultural productivity shocks – as proxied by exogenous annual rainfall deviations from long-term average – on education expenditures and children’s work status in rural Indian households. Our results show that a transitory increase in rainfall significantly reduces education expenditures and increases the likelihood of child labor across a range of work activities. Additionally, we show that productivity-enhancing inputs such as land ownership and credit access do not mitigate these countercyclical effects of rainfall variations, indicating the importance of market imperfections (in labor and land markets). We also find that the effects of productivity shocks are reinforced for historically marginalized castes, and moderated for more educated households. These highlight that the average effects mask considerable heterogeneity based on household and regional characteristics

International audience

International audience; This study aimed to examine Bradford's law of scattering on the global synthetic biology literature output published between 2005 to 2019. The authors used the publications data obtained from Web of Science database for the present study. The total data set consists of 8411 journal articles and 1453 journals. The authors employed both verbal and graphical formulations of Bradford's law. The author's calculated the value of Bradford's multiplier using Egge's formula and found it as 10.52. This analysis shows that a three-zone Bradford's distribution fits with the present data west with computed value Bardford's multiplier 10.52. A list of core journals covering around twelve journals also prepared.

International audience; This paper is based on the observations from Tamil Nadu. The presence of this critically endangered Theraphosidae, P. metallica has been recorded for the first time outside of its known distribution, wherefore, expanding its range to further south from its type locality. The present sighting extends its distribution ranges along the Eastern Ghats by approximately 370 Km to further south from its type locality (Pocock 1899).