A NOVEL APPROACH TOWARDS DEVELOPMENT OF QUINAZOLINE DERIVATIVES IN PAIN MANAGEMENT

ABSTRACT-   Objective: To synthesis evaluation of the analgesic and anti-inflammatory activities of pyrazoline bearing 4(3H)-quinazolinone derivatives. Methods: Synthesis of Chalcone (3a-3j) involves the Claisen-Schmidt condensation of equimolar quantities of substituted acetophenone with aromatic aldehyde in the presence of aqueous alkali (10%). Comp. (3a-3j) undergoes cyloaddition reaction with semicarbazide HCl in the presence of suitable solvent to yield comp. (4a-4j). It undergoes addition cyclization reaction with anthranillic acid to yield final comp. (6a-6j). Acute toxicity study of synthesized compound was found according to OECD guidelines 423. The test compound do not showed any toxicity up to 200mg/kg dose. Mortality was not observed during the course of study. The analgesic and anti-inflammatory activity of all synthesized compounds were carried by using hot plate method and Carrageenan induced Rat Paw Edema Method respectively. Results: All compounds synthesized are obtained in crystalline form with good practical yield. The purity and homogeneity of compounds synthesized were determined by sharp melting points and TLC method. The chemical structures were confirmed by FTIR, 1HNMR, and Mass spectrum. Conclusion: The synthesized compound 6b, 6d, 6e, 6i and 6j showed good analgesic and anti-inflammatory activities whereas others showed significant activities. Keywords: Quinazoline, pyrazole, analgesic and anti-inflammatory activity

Combining ability and heterosis analysis for fibre yield and quality parameters in roselle (Hibiscus sabdariffa L.)

Roselle (Hibiscus sabdariffa L.) is second important bast fibre crop after jute in India. With an aim to ex-ploit non-additive genetic variance present experiment was designed to identify good general combining parents and specific cross combination for fibre yield and fibre quality parameters (fibre fineness, fibre tenacity) in roselle. A total of 11 parents were crossed in complete diallel fashion which resulted 55 F1, 55 RF1 (reciprocal F1). Parents, F1s and RF1s were grown in randomized block design. Analysis of variance revealed significant differences (P< 0.01, P<0.05) among the parents and their hybrids. The parents AMV 1, AMV 5, GR 27 and AHS 160 were identified as good combiners since they recorded significant general combining ability (GCA) effects for fibre yield and quality parameters. Further, For fibre yield only three crosses (AMV 1 × AMV 4, AMV 1 × GR 27, HS 4288 × JRR 07) showed significant specific combining ability (SCA) effects from them hybrid AMV 1 × GR 27 (fibre yield=27.37g/ plant) exhibited positively significant best parent (Non bris 4, Mean fibre yield=21.16g/plant) heterosis (29.35%). Similarly, for fibre tenacity, hybrid GR 27 × JRR 07 (fibre tenacity=23.47g/tex) exhibited positively significant best parent (HS 4288; fibre tenacity=20.35g/tex) heterosis (15.30%)

Techno-economic viability of bio-based methyl ethyl ketone production from sugarcane using integrated fermentative and chemo-catalytic approach: process integration using pinch technology

Butanediols are versatile platform chemicals that can be transformed into a spectrum of valuable products. This study examines the techno-commercial feasibility of an integrated biorefinery for fermentative production of 2,3-butanediol (BDO) from sucrose of sugarcane (SC), followed by chemo-catalytic upgrading of BDO to a carbon-conservative derivative, methyl ethyl ketone (MEK), with established commercial demand. The techno-economics of three process configurations are compared for downstream MEK separation from water and co-product, isobutyraldehyde (IBA): (I) heterogeneous azeotropic distillation of MEK-water and extractive separation of (II) MEK and (III) MEK-IBA from water using p-xylene as a solvent. The thermal efficiency of these manufacturing processes is further improved using pinch technology. The implementation of pinch technology reduces 8% of BDO and 9–10% of MEK production costs. Despite these improvements, raw material and utility costs remain substantial. The capital expenditure is notably higher for MEK production from SC than BDO alone due to additional processing steps. The extraction based MEK separation is the simplest process configuration despite marginally higher capital requirements and utility consumption with slightly higher production costs than MEK-water azeotropic distillation. Economic analysis suggests that bio-based BDO is cost-competitive with its petrochemical counterpart, with a minimum gross unitary selling price of US$ 1.54, assuming a 15% internal rate of return over five-year payback periods. However, renewable MEK is approximately 16–24% costlier than the petrochemical route. Future strategies must focus on reducing feedstock costs, improving BDO fermentation efficacy, and developing a low-cost downstream separation process to make renewable MEK commercially viable

Effect of Mucin13 gene polymorphism on diarrhoeagenic <i>E. coli</i> adhesion pattern and its expression analysis in native Indian pigs

We identified genetic polymorphism in Mucin13 gene affecting E. coli adhesion patterns using (local isolate) diarrhoeagenic E. coli in Indian desi pigs. Five SNPs and one indel previously reported to be associated with enterotoxigenic E. coli (ETEC) F4ab/ac adhesion pattern were examined by designing PCR-RFLP protocol. The genotypic frequencies of only one SNP (g.22304A&thinsp; &gt; &thinsp;G) differed significantly (at P ≤ 0.05) in adhesive, non-adhesive and weakly adhesive population. The AA (306&thinsp;sbp, 231&thinsp;bp), AG (306, 231, 108, 198&thinsp;bp) and GG (231, 198&thinsp;bp, 108&thinsp;b) genotypes of g.22304A&thinsp; &gt; &thinsp;G locus were observed with frequencies 50.0&thinsp;%, 21.25&thinsp;% and 28.75&thinsp;%, respectively and AG genotype was significantly (P ≤ 0.05) associated with a non-adhesive pattern. The polymorphism information content of SNPs ranged from 17.67 (g.22124T&thinsp; &gt; &thinsp;C) to 37.36&thinsp;% (g.21471C&thinsp; &gt; &thinsp;T) loci. Three loci (g.21471C&thinsp; &gt; &thinsp;T, g.22124T&thinsp; &gt; &thinsp;C and g.22304A&thinsp; &gt; &thinsp;G) were significantly departed from Hardy–Weinberg equilibrium. The linkage disequilibrium analysis revealed locus g.22124T&thinsp; &gt; &thinsp;C and g.22304A&thinsp; &gt; &thinsp;G were significantly (P ≤ 0.05) associated with each other. Expression profiling of target gene in jejuna of animals having AA, AG and GG genotypes revealed differences in various genotypes with the highest in the AA, moderate in the GG and low levels in the AG genotype, although they were statistically non-significant (at P ≤ 0.05). The absence of significant effect of genotypes on MUC13 mRNA expression indicates no direct functional role, although the structural role can not be ignored as the putative receptor gene is located within targeted genomic region. Further, reports of same SNP association with an ETEC F4ab/ac adhesion pattern indicate the target gene's role in diarrhoea even caused by other strains of E. coli which is not ETEC.</p

Modern Machine Learning Tools for Monitoring and Control of Industrial Processes: A Survey

Over the last ten years, we have seen a significant increase in industrial data, tremendous improvement in computational power, and major theoretical advances in machine learning. This opens up an opportunity to use modern machine learning tools on large-scale nonlinear monitoring and control problems. This article provides a survey of recent results with applications in the process industry.Comment: IFAC World Congress 202

Revealing nature of GRB 210205A, ZTF21aaeyldq (AT2021any), and follow-up observations with the 4K×\times4K CCD Imager+3.6m DOT

Optical follow-up observations of optical afterglows of gamma-ray bursts are crucial to probe the geometry of outflows, emission mechanisms, energetics, and burst environments. We performed the follow-up observations of GRB 210205A and ZTF21aaeyldq (AT2021any) using the 3.6m Devasthal Optical Telescope (DOT) around one day after the burst to deeper limits due to the longitudinal advantage of the place. This paper presents our analysis of the two objects using data from other collaborative facilities, i.e., 2.2m Calar Alto Astronomical Observatory (CAHA) and other archival data. Our analysis suggests that GRB 210205A is a potential dark burst once compared with the X-ray afterglow data. Also, comparing results with other known and well-studied dark GRBs samples indicate that the reason for the optical darkness of GRB 210205A could either be intrinsic faintness or a high redshift event. Based on our analysis, we also found that ZTF21aaeyldq is the third known orphan afterglow with a measured redshift except for ZTF20aajnksq (AT2020blt) and ZTF19abvizsw (AT2019pim). The multiwavelength afterglow modelling of ZTF21aaeyldq using the afterglowpy package demands a forward shock model for an ISM-like ambient medium with a rather wider jet opening angle. We determine circumburst density of $n_{0}$ = 0.87 cm$^{-3}$, kinetic energy $E_{k}$ = 3.80 $\times 10^{52}$ erg and the afterglow modelling also indicates that ZTF21aaeyldq is observed on-axis ($\theta_{obs} < \theta_{core}$) and a gamma-ray counterpart was missed by GRBs satellites. Our results emphasize that the 3.6m DOT has a unique capability for deep follow-up observations of similar and other new transients for deeper observations as a part of time-domain astronomy in the future.Comment: Accepted for Special Issue of Journal of Astrophysics and Astronomy, 2022, Astrophysical jets and observational facilities: National perspective, 05 -09 April 2021, ARIES Nainita

Surface Nano-structured Coating for Improved Performance of Axial Piston Pumps

The work starts from the consideration that most of the power losses in a hydraulic pump is due to frictional losses made by the relative motion between moving parts. This fact is particularly true at low operating velocities, when the hydraulic lift effect must be able to maintain a minimum clearance in meatus to limit the volumetric losses. The potential of structured coatings at nanoscale, with super-hydrophobic and oleophobic characteristics, has never been exploited before in an industrial application. The work studies the potential application of nano-coating on piston slippers surface in a real industrial case. The aim is to develop a new industrial solution to increase the energetic efficiency of hydraulic pump used in earthmoving machines. The proposed solution is investigated using a dedicated test bench, designed to reproduce real working conditions of the pump. The results showa reduction of friction coefficient while changing working pressure and rotation velocity

Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study

Background Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country’s largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. Methods In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). Findings Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. Interpretation Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks

Novel spectrophotometric method for determination of cinacalcet hydrochloride in its tablets via derivatization with 1,2-naphthoquinone-4-sulphonate

This study represents the first report on the development of a novel spectrophotometric method for determination of cinacalcet hydrochloride (CIN) in its tablet dosage forms. Studies were carried out to investigate the reaction between CIN and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 8.5), an orange red-colored product exhibiting maximum absorption peak (λmax) at 490 nm was produced. The stoichiometry and kinetic of the reaction were investigated and the reaction mechanism was postulated. This color-developing reaction was employed in the development of a simple and rapid visible-spectrophotometric method for determination of CIN in its tablets. Under the optimized reaction conditions, Beer's law correlating the absorbance with CIN concentration was obeyed in the range of 3 - 100 μg/ml with good correlation coefficient (0.9993). The molar absorptivity (ε) was 4.2 × 105 l/mol/cm. The limits of detection and quantification were 1.9 and 5.7 μg/ml, respectively. The precision of the method was satisfactory; the values of relative standard deviations (RSD) did not exceed 2%. No interference was observed from the excipients that are present in the tablets. The proposed method was applied successfully for the determination of CIN in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 100.80 - 102.23 ± 1.27 - 1.62%. The results were compared favorably with those of a reference pre-validated method. The method is practical and valuable in terms of its routine application in quality control laboratories