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Depression is not similar to daily mood fluctuations and temporary emotional responses to day‐to‐day activities. Depression is not a passing problem; it is an ongoing problem. It deals with different episodes consisting of several symptoms that last for at least 2 weeks. It can be seen for several weeks, months, or years. At its final stage, or can say, in its worst condition, it can lead to suicide. Antidepressants are used to inhibit the reuptake of the neurotransmitters by some selective receptors, which increase the concentration of specific neurotransmitters around the nerves in the brain. Drugs that are currently being used for the management of various types of depression include selective serotonin reuptake inhibitors, tricyclic antidepressants, atypical antidepressants, serotonin, noradrenaline reuptake inhibitors, etc. In this review, we have outlined different symptoms, causes, and recent advancements in nitrogen‐containing heterocyclic drug candidates for the management of depression. This article highlights the various structural features along with the structure–activity relationship (SAR) of nitrogen‐containing heterocyclics that play a key role in binding at target sites for potential antidepressant action. The in silico studies were carried out to determine the binding interactions of the target ligands with the receptor site to determine the potential role of substitution patterns at core pharmacophoric features. This article will help medicinal chemists, biochemists, and other interested researchers in identifying the potential pharmacophores as lead compounds for further development of new potent antidepressants. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a multifactorial neurological disorder and single target directed drugs have been found ineffective in the retardation or reversal of disease state. In last few years, multi‐targeting agents are being explored as drug strategy for the effective treatment of AD. A series of (4‐(pent‐4‐yn‐1‐yloxy)phenyl)‐2‐phenylpyrimidine derivatives has been synthesized and evaluated against monoamine oxidase (MAO) and acetylcholinesterase (AChE) enzymes. Most of the synthesized compounds were found to be potent inhibitors of MAO−A, MAO−B and AChE enzymes with IC50 values in low micromolar range. In the series, BD‐13 and BD‐14 were found to be the most potent dual inhibitors of MAO−A and AChE enzymes. BD‐13 showed MAO−A and AChE inhibition with IC50 values of 0.78±0.12 μM and 2.84±0.19 μM, respectively. Similarly, BD‐14 showed potent inhibition activities against MAO−A and AChE enzymes with IC50 values of 0.75±0.04 μM and 2.19±0.06 μM, respectively. In reversibility studies, BD‐13 and BD‐14 were found to be reversible inhibitors of both MAO−A and AChE enzymes. In the cytotoxicity studies, BD‐13 and BD‐14 were found to be non‐toxic to the SH‐SY5Y cells. In the molecular dynamic simulation studies of 30 ns, both the potent compounds were found to be thermodynamically stable in the active sites of MAO−A and AChE. Thus, BD‐13 and BD‐14 can be used as lead compounds for the development of more potent compounds for the effective treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a multifactorial neurological disorder involving complex pathogenesis. Single target directed drugs proved ineffective and since last few years' different pharmacological strategies including multi-targeting agents are being explored for the effective drug development for AD. A total of 19 dipropargyl substituted diphenylpyrimidines have been synthesized and evaluated for the monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibition potential. All the compounds were found to be selective and reversible inhibitors of MAO-B isoform. These compounds also displayed good AChE inhibition potential with IC 50 values in low micromolar range. AVB4 was found to be the most potent MAO-B inhibitor with IC 50 value of 1.49 ± 0.09 μM and AVB1 was found to be the most potent AChE inhibitor with IC 50 value of 1.35 ± 0.03 μM. In the ROS protection inhibition studies, AVB1 and AVB4 displayed weak but interesting activity in SH-SY5Y cells. In the cytotoxicity studies involving SH-SY5Y cells, both AVB1 and AVB4 were found to be non-toxic to the tissue cells. In the molecular dynamic simulation studies of 30 ns, the potent compounds were found to be quite stable in the active site of MAO-B and AChE. The results suggested that AVB1 and AVB4 are promising dual inhibitors and have the potential to be developed as anti-Alzheimer's drug. Multi-potent compounds targeting MAO and AChE enzymes. Image 1 • A series of 4,6-diphenylpyrimidine derivatives designed as multipotent agents against AD. • Most of the compounds showed moderate to good inhibitory activities against MAO-B as well as AChE enzymes. • Compounds AVB1 and AVB4 displayed reversible inhibition of MAO-B and AChE along with ROS inhibition potential. • Compounds showed mixed type of inhibition of AChE as it bind to CAS as well as PAS. [ABSTRACT FROM AUTHOR]

A number of pyrimidine bridged combretastatin derivatives were designed, synthesized and evaluated for anticancer activities against breast cancer (MCF-7) and lung cancer (A549) cell lines using MTT assays. Most of the synthesized compounds displayed good anticancer activity with IC 50 values in low micro-molar range. Compounds 4a and 4p were found most potent in the series with IC 50 values of 4.67 µM & 3.38 µM and 4.63 µM & 3.71 µM against MCF7 and A549 cancer cell lines, respectively. Biological evaluation of these compounds showed that selective cancer cell toxicity ( in vitro using human lung and breast cancer cell lines) might be due to the inhibition of antioxidant enzymes instigating elevated ROS levels which triggers intrinsic apoptotic pathways. These compounds were found nontoxic to the normal human primary cells. Compound 4a , was found to be competitive inhibitor of colchicine and in the tubulin binding assay it showed tubulin polymerization inhibition potential comparable to colchicine. The molecular modeling studies also showed that the synthesized compounds fit well in the colchicine-binding pocket. [ABSTRACT FROM AUTHOR]

Chitosan-supported copper (chit@copper) based heterogeneous catalysts have been explored for A 3 -coupling and decarboxylative A 3 -coupling. The developed protocol employs low catalyst loading, solventless condition and easy work-up for the synthesis of diversely substituted propargylamines. More importantly, the catalyst could be recovered and reused without any significant loss in the activity. This offer huge advantages as recyclability issues are rarely addressed in decarboxylative A 3 -coupling. Leaching studies were carried out using AAS and ICPMS analysis. It is envisaged that chit@copper catalysts can have potential applications in terms of efficiency and recyclability in the emerging area of decarboxylative C H bond activation/functionalization strategies. [ABSTRACT FROM AUTHOR]

Monoamine oxidase inhibitors (MAOIs) are potential drug candidates for the treatment of various neurological disorders like Parkinson’s disease, Alzheimer’s disease and depression. In the present study, two series of 4-substituted phenylpiperazine and 1-benzhydrylpiperazine ( 1 – 21 ) derivatives were synthesized and screened for their MAO-A and MAO-B inhibitory activity using Amplex Red assay. Most of the synthesized compounds were found selective for MAO-B isoform except compounds 3 , 7 , 8 , 9 and 13 (MAO-A selective) while compound 11 was non-selective. In the current series, compound 12 showed most potent MAO-B inhibitor activity with IC 50 value of 80 nM and compound 7 was found to be most potent MAO-A inhibitor with IC 50 value of 120 nM and both the compounds were found reversible inhibitors. Compound 8 was found most selective MAO-A inhibitor while compound 20 was found most selective inhibitor for MAO-B isoform. In the cytotoxicity evaluation, all the compounds were found non-toxic to SH-SY5Y and IMR-32 cells at 25 µM concentration. In the ROS studies, compound 8 (MAO-A inhibitor) reduced the ROS level by 51.2% while compound 13 reduced the ROS level by 61.81%. In the molecular dynamic simulation studies for 30 ns, compound 12 was found quite stable in the active cavity of MAO-B. Thus, it can be concluded that phenyl- and 1-benzhydrylpiperazine derivatives are promising MAO inhibitors and can act as a lead to design potent, and selective MAO inhibitors for the treatment of various neurological disorders. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel series of substituted- N -(5,6-diphenyl-1,2,4-triazin-3-yl) benzamide (R: 1 - R: 10) were designed and synthesized. • Two compounds (R:5 and R: 9) showed most potent MAO-A inhibition activity. • Compounds R: 5 and R: 9 showed noteworthy antidepressant-like effect. • In ADME studies none of the compounds violated the lipinski rule and all other parameters were also within the acceptable ranges. The novel series of substituted- N -(5,6-diphenyl-1,2,4-triazin-3-yl) benzamides (R: 1 – 12) were designed, synthesized and evaluated for in-vitro and in-vivo antidepressant-like activity. In MAO-A inhibition assay, compound R: 5 and R: 9 displayed most potent activity with IC 50 = 0.12 and 0.30 µM. R: 5 and R: 9 were also evaluated for in-vivo antidepressant using FST and TST. In both models, the test samples R: 5 and R: 9 showed noteworthy antidepressant effect. R: 5 showed 46.48 % and 45.96 % reduction in immobility in FST and TST respectively at dosage of 30 mg/kg (p.o). Whereas compound R: 9 reduced the immobility time by 52.76 % and 47.14 % as compared to control in FST and TST, respectively at same dosage. Both the compounds were also tested for behavioural study using actophotometer and grip tests. None of compounds exhibited decrease in locomotor activity. Further, these compounds were subjected to in silico studies to determine their ADME properties along with binding energies and binding orientions. In ADME studies none of the compounds violated the Lipinski rule and all other parameters were also within the acceptable ranges. In docking study R: 5 (-10.7) and R: 9 (-10.4) were also displayed highest docking score. These encouraging results present the pharmacophoric features of substituted- N -(5,6-diphenyl-1,2,4-triazin-3-yl) benzamides as interesting lead for further development of new antidepressant drug molecules. [ABSTRACT FROM AUTHOR]

Highlights: [•] Macroscopic and molecular level interactions of imidazolium ionic liquids in ethylene glycol have been determined. [•] and Δκ S are positive over the whole composition range for all investigated mixtures. [•] Multiple hydrogen bonding interactions existing between unlike constituents in mixtures of varying strengths. [ABSTRACT FROM AUTHOR]

Abstract: Physical properties such as densities and speeds of sound of 1-hexyl-3-methylimmidazolium based room temperature ionic liquids (RTILs); with bromide (Br), tetrafluoroborate (BF4), hexafluorophosphate (PF6), as anions in ethylene glycol monomethyl ether (EGMME), over the whole composition range were measured at T =(288.15–318.15)K and at atmospheric pressure. Experimental densities were used to obtain excess molar volumes, V E . The V E values for each of the mixture studied were negative and decreased with increase in temperature with the following order: [PF6]>[BF4]>[Br]. Deviations in isentropic compressibility, Δκ S were calculated from the experimental speeds of sound and densities. The Δκ S values were negative over the entire range of composition for all mixtures with the exception of ILs containing [Br] and [BF4] anions, which changes sign from negative to positive at low temperatures. Both V E and Δκ S were fitted to the Redlich–Kister polynomial equation to obtain the binary coefficients and the standard errors. The molecular scale interactions between (ILs) and EGMME were investigated through 1H NMR spectroscopy. NMR chemical shifts for various protons of (ILs) or EGMME molecules and their deviations show hydrogen bonding interactions of varying strengths between (ILs) and EGMME in their binary mixtures. [Copyright &y& Elsevier]

Abstract: The thermodynamic behaviour of imidazolium based ionic liquids (ILs), 1-butyl-3-methylimidazolium chloride [C4mim][Cl]; 1-octyl-3-methylimidazolium chloride [C8mim][Cl], and 1-butyl-3-methylimidazolium methylsulfate [C4mim][C1OSO3] in ethylene glycol [HOCH2CH2OH] (EG) have been investigated over the whole composition range at T =(298.15 to 318.15)K to probe the interactions in bulk. For the purpose, volumetric properties such as excess molar volume, , apparent molar volume, Vϕ , i , and its limiting values at infinite dilution, , have been calculated from the experimental density measurements. The molecular scale interactions between ionic liquids and EG have been investigated through Fourier transform infrared (FTIR) and 1H NMR spectroscopy. The shift in the vibrational frequency for C–H stretch of aromatic ring protons of ILs and O–H stretch of EG molecules has been analysed. The NMR chemical shifts for various protons of RTILS or EG molecules and their deviations show multiple hydrogen bonding interactions of varying strengths between RTILs and EG in their binary mixtures. [Copyright &y& Elsevier]

Abstract: Densities and speeds of sound have been measured for the binary mixtures of ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate [bmim][PF6] with ethylene glycol monoethyl ether (EGMEE), diethylene glycol monoethyl ether (Di-EGMEE), triethylene glycol monoethyl ether (Tri-EGMEE) over the whole composition range at atmospheric pressure. Experimental densities have been used to estimate excess molar volumes, V E . Changes in isentropic compressibility, Δκ s have been estimated by using experimental speed of sound and density values. Excess properties were fitted to the Redlich–Kister polynomial equation to obtain the binary coefficients and the standard errors. The molecular scale interactions between ionic liquid and alkoxyalkanols have been investigated through 1H NMR spectroscopy. NMR chemical shifts for hydroxyl group of alkoxyalkanols and their deviations show hydrogen bonding interactions of varying strengths between ionic liquid and alkoxyalkanol in their binary mixtures. [Copyright &y& Elsevier]

[Display omitted] • Sodium channel inhibitors are the promising target for the management of convulsions. • Detailed pharmacology of sodium channel. • Development of anticonvulsant drugs as voltage gated sodium channel inhibitors. • Detailed pharmacological activity, SAR and possible mechanisms is discussed. Voltage-gated sodium channel blockers are one of the vital targets for the management of several central nervous system diseases, including epilepsy, chronic pain, psychiatric disorders, and spasticity. The voltage-gated sodium channels play a key role in controlling cellular excitability. This reduction in excitotoxicity is also applied to improve the symptoms of epileptic conditions. The effectiveness of antiepileptic drugs as sodium channel depends upon the reversible blocking of the spontaneous discharge without blocking its propagation. There are number of antiepileptic drug(s) which are in pipeline to flour the market to conquer abnormal neuronal excitability. They inhibit the seizures through the inhibition of complex voltage- and frequency-dependent ionic currents through sodium channels. Over the past decade, the sodium channel is one of the most explored targets to control or treat the seizure, but there has not been any game-changing discovery yet. Although there are large numbers of drugs approved for the treatment of epilepsy, however they are associated with several acute to chronic side effects. Many research groups have tirelessly worked for better therapeutic medication on this popular target to treat epileptic seizures. The review quotes briefly the developments of the approved examples of sodium channel blockers as anticonvulsant drugs. Medicinal chemists have tried the design and development of some more potent anticonvulsant drugs to minimize the toxicity that are discussed here, and an emphasis is given for their possible mechanism and the structure–activity relationship (SAR). [ABSTRACT FROM AUTHOR]

Cancer is a growing problem that has not yet been fully harnessed. Frequent mutations make this a highly variable and challenging pathology. Interestingly, mitochondria have currently emerged as a new target for cancer therapy. A group of agents with anticancer activity, termed mitocans that encourage apoptosis through mitochondrial disruption is currently important in research. From conventional glycolytic inhibitors to recent radiolabeled compounds, mitochondrial‐targeted therapies have marked their presence in cancer. Several TCA cycle and OXPHOS inhibitors are being established for their possible anticancer properties. There are so many distinctive differences in mitochondrial structure and function between normal and cancer cells that offer the potential for the clinical use of mitochondria as targets for novel and site‐specific anticancer agents. Mitochondrial targeting can be made possible if the bioactive molecule is specifically and selectively delivered to the mitochondria of the correct cell type using cell‐specific ligands and mitochondriotropic molecules. [ABSTRACT FROM AUTHOR]

An Indian traditional medicinal plant, Boerhaavia diffusa (Punarnava), is reported for its diuretic activity and helps in impaired kidney function. The present study indicates that alkaloids, carbohydrates, saponins, phytosterols, flavonoids, and glycosides are absent in the petroleum ether extract and present chiefly in the methanolic extract of roots. The phytosterols were found to be present in the ethyl acetate extract, while other phytochemical constituents, that is, alkaloids, carbohydrates, saponins, flavonoids, and glycosides, were absent. From high‐performance thin‐layer chromatography, the results indicated that out of all the three extracts and two marketed formulations, ethyl acetate root extract (LEA) has the highest amount of Boeravinone B content. Further, different root extracts of B. diffusa and two marketed formulations were evaluated on the human embryonic kidney cell line to understand pharmacological safety. From the results, it was observed that LEA and petroleum ether root extracts showed a higher percentage of cell survival and a better safety profile up to the dose of 1 mg/mL. The overall results indicated that further preclinical evaluation of B. diffusa is needed to understand the mechanism behind nephroprotective potential which can further expedite the drug discovery process of nephroprotective molecules. [ABSTRACT FROM AUTHOR]

Review: 147 refs. [ABSTRACT FROM AUTHOR]

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

Bathua (Chenopodium album) is a rich source of extensive-ranging nutrients, including bio-active carbohydrates, flavonoids and phenolics, minerals, and vitamins that translate to countless health benefits such as anticancer, antidiabetic, anti-inflammatory, antimicrobial, and antioxidant activity. Ascaridole, an important phytoconstituent present in aerial parts of the plant, contributes to its anthelmintic property. Even with vast historical use and significant health benefits, its renown has not spread, and utilization has significantly decreased in recent decades. Gradually, the plant has become known under the name of Non-conventional edible plant (NCEP). This compilation is prepared to bring out the plant under the spotlight for further research by foregrounding previous studies on the plant. Scientific research databases, including PubMed, Google Scholar, Scopus, SpringerLink, ScienceDirect, and Wiley Online, were used to fetch data on C. album. This review offers over up-to-date knowledge on nutritious values, phytochemical composition, volatile compounds, as well as health benefits of C. album. The ethnobotanical and ethnomedicinal uses of the plant in India and other parts of the world are deliberately discussed. Scrutinizing the reported literature on C. album reveals its powerful nutrient composition advantageous in the development of food products. The impact of various cooking and processing methods on the nutritional profile and bioavailability are discussed. The future perspectives with regards to the potential for food and nutraceutical products are critically addressed. This review proves the necessity of breakthrough research to investigate the pharmacology and safety of phytochemicals and nutraceutical development studies on the C. album. [ABSTRACT FROM AUTHOR]

Pyrimidine itself or in different fused forms is an important chemical motif for every step of cell life. Alongside, it exists as a key pharmacophoric part in thiamine, alloxan, orotic acid, and other isoforms of nucleotide bases. It has emerged as a privileged scaffold in medicinal chemistry due to its various possible structural and pharmacological attributes. In a number of clinically used chemical agents, pyrimidine or its fused/clubbed form with other moieties act as a key pharmacophore. Structure activity relationship (SAR) studies of the explored derivatives demonstrated that slight modifications with various substitutions on the pyrimidine rings can deviate biological activity to a large extent. 2‐Pyrimidone and 2,4‐pyrimidione derivatives are largely explored by a number of research groups for various pharmacological targets and due to their similarity to nucleotide bases, it has a great impact on the biological profile of these molecules. The current review focuses on describing the recent advancements (2015 onward) in the development of pyrimidine‐based biologically active molecules along with drug candidates under different clinical trials. The aim of this review is to provide structural features associated with pyrimidine along with their SAR studies, which are believed to be valuable for the scientists working on the development of pyrimidine‐based small molecules in the aforementioned disease conditions. We believe that the results of this research will help to provide a structural idea that may be used in the design and development of new pyrimidine‐based small molecules that target a variety of receptors or enzymes. [ABSTRACT FROM AUTHOR]

Cancer represents one of the world's biggest hazardous diseases. p53 is the uttermost researched tumour suppressor protein. It is commonly considered the "guardian of the genome," performing a critical function in genetic stability maintenance through controlling the cell cycle, programmed cell death, DNA repair, aging, and angiogenesis. The abnormalities in p53 lead to genetic instability and plays a significant role in carcinogenesis. The role of p53 in tumour suppression is emphasized in addition by the observation that primary silencing with this protein occurred in more than 50% of cancers. MDM2, p53, and the p53-MDM2 connections are well-known targets for the prevention and treatment of cancer. Moreover, in tumors with wild-type p53, their efficacy is decreased due to MDM2 enlargement or by the gradual decrease of MDM2 blocker ARF. As a result, improving p53 activity in cancerous cells provides a promising anticancer strategy. Various techniques are now being investigated, and addressing the p53-MDM2 interaction had also evolved as a potentially feasible strategy for contending with tumors. Both p53 and MDM2, interact via an autoregulation response signal: p53 activity induces MDM2 transcription, which in response interacts with p53's N-terminal transactivation domain, inhibiting its transcriptional activity. This article provides information on the current scenario of anti-tumor activities, with a particular emphasis on structure-activity relationship characteristics (SAR) against the p53-MDM2 to treat cancer. The primary purpose of this review is to cover recent advancements in the creation and testing of anticancer drugs that target the p53-MDM2 structure. This review contains different heterocyclic moieties which show significant results toward cancer. A mechanistic route is shown here, demonstrating both normal and malignant conditions via several stressed factors. Several compounds entered clinical trials as p53-MDM2 inhibitors for the treatment of cancer. [Display omitted] • p53, "guardian of the genome," abnormalities play a significant role in carcinogenesis. • p53 primary silencing is in more over 50% of cancers and potential target of cancer. • This manuscript emphasis on SAR against the p53-MDM2 to treat cancer. • It covers recent advancements in the creation and testing of anticancer drugs targeting p53-MDM2. [ABSTRACT FROM AUTHOR]

Volumetric and ultrasonic properties of ionic liquids (ILs), 1-butyl-3-methylimidazolium tetrafluoroborate [C 4 mim][BF 4 ], 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide [C 4 mim][NTf 2 ] and 1-butyl-3-methylimidazolium methylsulfate [C 4 mim][C 1 OSO 3 ] with 1,2-propanediol (1,2-PD) have been investigated using density, ρ speed of sound, u measurements over the entire composition range at T = (293.15, 298.15, 303.15, 308.15, 313.15, and 318.15) K. The density values were used to calculate excess molar volume, V m E whereas speed of sound results have been used to calculate deviation in isentropic compressibility, Δ κ S . Excess properties have been fitted to the Redlich-Kister polynomial equation to obtain the binary coefficients and the standard deviations. Spectroscopic technique like Fourier transform infrared (FT-IR) has been utilized for analyzing molecular level interaction prevailing between the binary mixtures. FT-IR technique has been used to scrutinize the –OH interactions between the binary mixtures and the influence on the structural variations in the ionic liquid. The excess properties and spectroscopic data have been analyzed in terms of the effect of temperature and the change of the anion of ionic liquid. [ABSTRACT FROM AUTHOR]

The current anti‐inflammatory drugs are associated with various severe adverse or side effects which mark the question on long term clinical use of such medications. These factors necessitate the development of new heterocyclic molecules having anti‐inflammatory potential with minimal to no adverse effect or toxicity. In continuation to our work, in herein report design and synthesis of a series of 15 indole‐3‐subtituted isoxazoles having potential anti‐inflammatory as well as analgesic properties. Most of the compounds exhibited comparable in‐vivo anti‐inflammatory and analgesic activity in rats to the reference drugs. Compound 9 d, 9 f and 9 i were found to show most significant anti‐inflammatory activity and reduced the paw edema by 67.74 %, 61.29 %, and 77.42 % respectively which were comparable to reference drug indomethacin. The COX inhibition studies reveled that these compounds have 2–3 folds selectivity for COX‐2 with moderate inhibition activity. In final, molecular docking studies were performed to understand the mechanistic and binding modes at catalytic active sites of COX‐2. The results revealed good selectivity of compounds for COX‐2 preferably over other inflammatory targets. The compound 9 i is obtained as lead molecule from the current series as promising structural feature for further development of novel anti‐inflammatory agent. [ABSTRACT FROM AUTHOR]

Abstract: The densities, ρ and the speeds of sound, u, for binary liquid mixtures of 1,4-dioxane with 1-propanol, 2-propanol, 1-butanol, and 2-butanol have been measured as a function of composition using an Anton-Paar DSA 5000 densimeter at temperatures (293.15, 298.15, 303.15 and 308.15) K and atmospheric pressure. The excess molar volumes, VE , and excess molar isentropic compressibilities, K S,m E , were calculated from the experimental data. The computed quantities were fitted to Redlich–Kister equation to derive the coefficients and estimate the standard error values. Also, apparent molar volume, V ϕ,i and partial molar volume, , excess partial molar volume, and their limiting values at infinite dilution, , and respectively have been calculated from the experimental density measurements. Excess partial molar isentropic compression, K S,i E , of both components and their respective limits at infinite dilution, K S,i E,∞ ,were analytically obtained using Redlich–Kister type equations. The variation of these properties with composition and temperature of the mixtures are discussed in terms of molecular interactions. [Copyright &y& Elsevier]

Abstract: The interactions of alkoxyalkanols with the ionic liquid 1-butyl-3-methylimidazolium bromide [bmim][Br] as a function of temperature were investigated by combination of volumetric and acoustic methods. The density, ρ, and speed of sound, u, of ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, and triethylene glycol monomethyl ether (0.00–1.01mol·kg−1) in aqueous 1-butyl-3-methylimidazolium bromide solutions ranging from pure water to 0.29mass% of ionic liquid have been measured at T =(288.15, 298.15 and 308.15)K and atmospheric pressure. The apparent molar volume (Vϕ ) and adiabatic compressibility (Kϕ , S ) of alkoxyalkanols in aqueous ionic liquid solution were determined at the measured temperatures. The partial molar volume and partial molar adiabatic compressibility of alkoxyalkanols at infinite dilution were evaluated. Transfer volumes and transfer adiabatic compressibility () at infinite dilution from water to aqueous ionic liquid solution were also calculated. The temperature dependence of the apparent molar volume was used to calculate apparent molar expansivity () and the Hepler’s constant values, . The results were explained on the basis of competing patterns of interactions of co-solvent and the solute. [Copyright &y& Elsevier]

Background & objectives: Serology testing is essential for immunological surveillance in the population. This serosurvey was conducted to ascertain the cumulative population immunity against SARS-CoV-2 among adults in Jammu district and to understand the association of seropositivity with sociodemographic and clinical correlates. Methods: On September 30 and October 1, 2020, a household survey was done in 20 villages/wards chosen from 10 health blocks in district Jammu, India. Demographic, clinical and exposure information was collected from 2000 adults. Serum samples were screened for IgG antibodies using COVID Kavach MERILISA kit. Tests of association were used to identify risk factors associated with IgG positivity. Crude odds ratio with 95 per cent confidence intervals (CIs) was calculated during univariate analysis followed by logistic regression. Results: Overall adjusted seroprevalence for SARS-CoV-2 was 8.8 per cent (95% CI: 8.78-8.82); it varied from 4.1 per cent in Chauki choura to 16.7 per cent Pallanwalla across 10 blocks in the district. Seropositivity was observed to be comparatively higher in 41-50 and 61-70 yr age groups, among males and in rural areas. Fever, sore throat, cough, dyspnoea, myalgias, anosmia, ageusia, fatigue, seizures, history of exposure, medical consultation, hospitalization and missing work showed significant association with seropositivity on univariate analysis. On logistic regression, only sore throat, myalgia and missing work showed significant adjusted odds of IgG positivity. Extrapolation to adult population suggested that exposure to SARS-CoV-2 was 14.4 times higher than reported cases, translating into Infection fatality rate of 0.08 per cent. Interpretation & conclusions: Since a major part of population was immunologically naive, all efforts to contain COVID-19 need to be vigorously followed while these baseline results provide an important yardstick to monitor the trends of COVID-19 and guide locally appropriate control strategies in the region. [ABSTRACT FROM AUTHOR]

Depression is declared the second leading cause of disability worldwide. Recently, cases of depression have increased significantly in adolescents, young adults as well as in elder population. Monoamine oxidase‐A (MAO‐A) is considered one of the major targets for the treatment of depression. In the current study, we have designed and synthesized various indole functionalized piperazinyl derivatives and evaluated them for in vitro MAO‐A inhibitory activity and in vivo antidepressant‐like activity. Most of the compounds were found to possess potent MAO‐A inhibitory activity with IC50 values in the sub‐micromolar range along with significant selectivity over MAO‐B. Compounds RP1 and RP9 emerged as the most promising reversible MAO‐A inhibitors with IC50 values of 0.11±0.03 μM and 0.14±0.02 μM and displayed selectivity of 193 folds and 178 folds over Monoamine oxidase‐B (MAO‐B), respectively. In the series, RP1 showed good intracellular ROS inhibitory activity along with neuroprotective properties. These compounds were found nontoxic against SH‐SY5Y cells and explored antidepressant activities. In the in vivo Forced swimming test (FST) and Tail suspension test (TST) studies, RP1 exhibited potential antidepressant‐like behavior similar to standard drug fluoxetine while compound RP9 showed antidepressant‐like activity only in the TST studies. The molecular docking and dynamics studies further supported the results obtained in the in vitro and in vivo studies. Thus, the indole functionalized piperazinyl derivatives were found to be promising ligands and can be developed as new antidepressant molecules. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new series of oxadiazole clubbed benzhydrylpiperazines (AP1-12) was designed, synthesized and evaluated for MAO inhibitory potential. • In this series, compounds AP3 and AP12 displayed most potent, selective and reversible inhibition of MAO-A enzyme. • In FST and TST studies, AP3 and AP12 exhibited potential antidepressant-like behaviour similar to standard drug fluoxetine. • Both potent compounds displayed good binding affinity and stability at binding pocket of MAO-A in in silico studies. Arylpiperazine clubbed various heterocyclic molecules present potential pharmacophoric structural features for the development of psychoactive drugs. There are various CNS active molecules possessing arylpiperazine moiety in their pharmacophore approved by USFDA. In the current study, we have explored the benzhydrylpiperazine moiety clubbed with various substituted oxadiazole moieties (AP1-12) for their monoamine oxidase (MAO) inhibition and antidepressant potential. Compounds AP3 and AP12 exhibited highly potent and selective MAO-A inhibition with IC 50 values of 1.34 ± 0.93 µM and 1.13 ± 0.54 µM, respectively, and a selectivity index of 10- and 13-folds, respectively. Both the compounds displayed reversible binding character at the active site of MAO-A. In further in vivo evaluation, both the compounds AP3 and AP12 displayed potential antidepressant-like character in FST and TST studies via significantly reduced immobility time in comparison to non-treated animals. These compounds displayed no cytotoxicity in SH-SY5Y cell lines, which indicates that these compounds are safe for further evaluation. In silico studies reveal that synthesized compounds possess drug-likeness with minimal to no toxicity. In silico studies were conducted to understand the binding interactions and stability of compounds at the binding pocket of enzyme and observed that both the best compounds fit well at the active site of MAO-A lined by amino acid residues Tyr69, Asn181, Phe208, Ile335, Leu337, Phe352, and Tyr444 similar to standard MAO-A inhibitor clorgiline. The molecular dynamic studies demonstrated that AP3 and AP12 formed quite a stable complex at the active site of MAO-A and did not break under small abruption forces. The favourable binding interactions and appropriate ADMET properties present the benzhydrylpiperazine clubbed oxadiazole pharmacophoric features as a potential structural skeleton for further clinical evaluation and development of a new antidepressant drug molecule. [ABSTRACT FROM AUTHOR]

Carbon has always found a spotlight in human life either in the form of graphite, diamonds, activated charcoal, carbon nanotubes, or carbon dots (CDs). Carbon quantum dots (CQDs) or CDs became the centre of attraction because of their potential applications in biomedical field such as bio‐imaging, drug nanocarriers, gene therapeutics, photosensitizing agents, theranostics and provides other multifunctional diagnostic platforms. There are numerous advantages of CDs due to their biocompatibility, reduced toxicity, water‐solubility, ease of scale‐up, and, most notably their fluorescence properties contrary to other carbon nanostructures. In last few years, significant efforts have been put by various research teams to synthesize and develop nanostructured materials possessing specific functional properties and characteristics. This work focus on the recent developments in the synthetic approaches applied for CDs using environment‐friendly sources. This review also highlights the mechanistic aspects, applications of CDs in biomedicine and a multi‐sensing platform along with challenges and future perspectives of this promising field. The authors believe that this review will help audible researchers to select a suitable environment‐friendly approach for the synthesis of CDs from green sources with required functions and properties. It will also guide researchers to develop a more convenient, efficient, and environment‐friendly method for the synthesis of new tunable carbon dots. [ABSTRACT FROM AUTHOR]

Inflammation is the human body's defence process against various pathogens, toxic substances, irradiation, and physically injured cells that have been damaged. Inflammation is characterized by swelling, pain, redness, heat, as well as diminished tissue function. Multiple important inflammatory markers determine the prognosis of inflammatory processes, which include likes of pro-inflammatory cytokines which are controlled by nuclear factor kappa-B (NF-kB), mitogen-activated protein kinase (MAPK), Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway, all of which are activated in response to the stimulation of specific receptors. Besides these, the cyclooxygenase (COX) enzyme family also plays a significant role in inflammation. The current review is kept forth to compile a summary of small molecules-based drugs approved by the USFDA during the study period of 2013–2023. A thorough discussion has also been made to focus on biologics, macromolecules, and small chemical entities approved during this study period and their greener synthetic routes with a brief discussion on the chemical spacing parameters of anti-inflammatory drugs. The compilation is expected to assist the medicinal chemist and the scientist actively engaged in drug discovery and development of anti-inflammatory agents from newer perspectives during the current years. The current review is kept forth to compile a summary of small molecules-based drugs approved by the USFDA during the study period of 2013–2023. [Display omitted] • Inflammatory markers determine the prognosis of inflammatory processes and its severity. • Various molecular mechanisms and its mediators are enlisted in this review. • This review majorly focusses on small molecules-based drugs approved by the USFDA (2013–2023). • The compilation is expected to provide newer perspectives to scientific community in drug discovery and development of anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new series of oxadiazole clubbed piperazines (5a-j) was designed, synthesized and evaluated for MAO inhibitory potential. • In this series, compounds 5f and 5 g displayed most potent, selective and reversible inhibition of MAO-A enzyme. • These compounds also exhibited neuroprotective and free radical scavenging potential without toxicity against SH-SY5Y cells. • In FST and TST studies, 5f and 5 g exhibited potential antidepressant-like behaviour similar to standard drug fluoxetine. Piperazine derivatives have been of great interest to medicinal chemists in the development of antidepressant drugs due to their distinct molecular and structural features along with their pharmacological profile. In this study, we have designed and synthesized a series of 10 compounds of piperazine clubbed oxadiazole derivatives (5a-j) and screened for their MAO inhibitory activity. Compound 5f and 5 g were found to be the most potent MAO-A inhibitors of the series with IC 50 values of 0.96 ± 0.04 µM µM and 0.81 ± 0.03 µM, respectively with a selectivity index of 18-folds and 9-folds over MAO-B isoform. The compounds were found to be reversible inhibitors of MAO-A with no cytotoxicity against SH-SY5Y neuronal cells. The compounds also displayed good antioxidant activity. Further, in vivo TST studies revealed that both the compounds 5f and 5 g possessed good anti-depressant-like activity and reduced the immobility time significantly although were found inactive in FST studies. The molecular docking studies revealed that both compounds fit well at the active site of MAO-A enzyme as similar to clorgyline and form a stable complex. The results were confirmed via molecular dynamic studies which demonstrate the stable complex formation between MAO-A and 5f & 5 g. The appropriate drug-like characteristics with favourable ADMET profile, these molecules presented this piperazine clubbed oxadiazole structural framework as a key pharmacophore for the development of new antidepressant molecules along with strong candidature for further clinical investigations. [ABSTRACT FROM AUTHOR]

Turcicum leaf blight of maize caused by the fungus Setosphaeria turcica is a serious foliar disease of maize distributed widely throughout the world and causing significant yield losses. The disease is more prevalent in humid weather with temperature between 20-28 °C and causes small cigar-shaped lesions to complete destruction of the foliage. Though there are several management practices available, identification and deployment of host plant resistance is a pragmatic approach to control the disease. However, qualitative resistance is unstable and breaks down easily by emergence of new races of the pathogen in maize necessitating the development of durable TLB resistant cultivars. Application of modern molecular tools and availability of high-density molecular marker data are expected to accelerate efforts to develop resistant hybrids. This review provides a focuses on current status, and future research needs especially biological control and sustainable integrated management strategies of TLB. [ABSTRACT FROM AUTHOR]

• A series of substituted benzenesulfonyl piperazine (NP1-NP16) derivatives was synthesized and screened for their MAO inhibitory activity. • Compounds NP4 and NP12 were found to be most potent, selective and reversible inhibitors of MAO-A enzyme. • The compounds showed neuroprotective and antioxidant properties without any toxicity against SH-SY5Y cells. • In FST and TST studies, NP4 and NP12 exhibited potential antidepressant-like behavior similar to standard drug fluoxetine. Monoamine oxidase-A inhibitors (MAO-AIs) are potential drug candidates for the treatment of depression. In the present study, a series of substituted benzenesulfonyl piperazine (NP1-NP16) derivatives was synthesized and screened for their MAO-A and MAO-B inhibitory activity using the Amplex Red assay. Most of the synthesized compounds were found to show selective inhibition of MAO-A isoform. Compounds NP4 and compound NP12 showed the most potent MAO-A inhibitor activity with IC 50 values of 0.25 ± 0.04 μM and 0.46 ± 0.02 μM, respectively, and both the compounds were found reversible inhibitors. Compound NP4 was found most selective as an MAO-A inhibitor with a selectivity of 52 folds over the MAO-B isoform. In the cytotoxicity evaluation, the compounds were found nontoxic to SH-SY5Y cells and also exhibited neuroprotective properties. In the DPPH studies, compounds NP4 and NP12 showed free radical scavenging activity via reducing absorbance by around 50% at a concentration of 1 mM. In the in vivo Forced swimming test (FST) studies, NP4 and NP12 exhibited potential antidepressant-like behavior similar to standard drug fluoxetine while in the Tail suspension test (TST), both the compounds showed antidepressant-like activity better than the standard. The molecular docking studies further supported the results obtained in the in vitro and in vivo studies. Thus, the substituted benzenesulfonyl functionalized piperazinyl derivatives were found to be promising ligands and can be developed as new antidepressant molecules. [ABSTRACT FROM AUTHOR]

The potential for using natural polysaccharide based interpenetrating polymer network (IPN) as an adsorbent for the removal of oil from contaminated water was investigated in the present work. The IPN was used to absorb crude oil from waste water at various experimental conditions. The effect of different parametric conditions like adsorbent mass, time, temperature and mixing speed on adsorption of crude oil was studied. The maximum adsorption was observed at rotation speed of 500 rpm, temperature 40 °C, pH 3, contact time 60 min and crude oil concentration 0.030 g/L. The results revealed that crude oil adsorption with natural polysaccharide based biodegradable IPN is feasible due to its high affinity for oil, make the IPN important from technological and environmental view point. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CP) and its highly electrophilic intermediates are principal toxic metabolites. The active form of CP i.e. chlorpyrifos oxon (CP-oxon) is responsible for both the insecticidal activity and is also of greater risk when present in the atmosphere. Thus, the combined effects of both CP, CP-oxan, and other metabolites enhance our understanding of the safety and risk of the insecticide CP. They cause major toxicities such as AChE inhibition, oxidative stress, and endocrine disruption. Further, it can have adverse hematological, musculoskeletal, renal, ocular, and dermal effects. Excessive use of this compound results in poisoning and potentially kills a non-target species upon exposure including humans. Several examples of reactive metabolites toxicities on plants, aquatic life, and soil are presented herein. The review covers the general overview on reactive metabolites of CP, chemistry and their mechanism through toxic effects on humans as well as on the environment. Considerable progress has been made in the replacement or alternative to CP. The different strategies including antidote mechanisms for the prevention and treatment of CP poisoning are discussed in this review. The approach analyses also the active metabolites for the pesticide activity and thus it becomes more important to know the pesticide and toxicity dose of CP as much as possible. [Display omitted] • Chlorpyrifos and its electrophilic intermediates are highly toxic metabolites. • The degradation of chlorpyrifos mainly involves the oxidation, hydrolysis and diarylation. • The reactive metabolites induce toxicities via oxidative stress, AChE inhibition, and endocrine disruption. • The degradation products were toxic on humans, plants, aquatic life, and soil. • The different treatment strategies including antidote mechanism alleviates the symptoms of poisoning. [ABSTRACT FROM AUTHOR]

• A new series of triazine clubbed piperazine derivatives was synthesized. • Two compounds RP4, and (RP5) showed most potent anticonvulsant activity in both MES and scPTZ convulsion mice models. • The most active compound RP5 was effective at median doses (ED 50) of 14.82 mg/kg in MES and 14.61 mg/kg in scPTZ model. • In biochemical estimation, RP4 and RP5 were found nontoxic and showed no sign of any pathological changes in blood chemistry, liver, and nephrology of the kidney. The new series of N-(5,6-diphenyl-1,2,4-triazin-3-yl)-2-(4-substituted piperazin-1-yl) acetamide (RP1–5) and 2-((5,6-diphenyl-1,2,4-triazin-3-yl)thio)-1-(4- substituted piperazin-1-yl)-ethan-1-one (RP6–10) derivatives were designed and synthesised by clubbing substituted 5,6-diphenyl-1,2,4-triazine with different substituted piperazines. The synthesized compounds were tested for anticonvulsant activity and various biochemical toxicity parameters. Among the series, two compounds (2-(4-benzylpiperazin-1-yl)-N-(5,6-diphenyl-1,2,4-triazin-3-yl)acetamide (RP4), and 2‑chloro-1-(4-substituted piperazin-1-yl)ethan-1-one (RP5) were found to demonstrate the most potent anticonvulsant activity in both MES and scPTZ convulsion mice models. The most active compound RP5 was effective at median doses (ED 50) of 14.82 mg/kg in MES and 14.61 mg/kg in scPTZ model. The median toxic dose (TD 50) was > 600 which provided the compound RP5 with high protective index of 40.48 in the MES test and 41.06 in scPTZ test. Further, both the compounds were also found to possess significant antidepressant activity. The compounds did not show any adverse effect in various parameters such as grip-strength test (skeletal muscular strength), actophotometer, and rotarod test (locomotor) as compared to the control groups. In biochemical estimation, RP4 and RP5 were found nontoxic and showed no sign of any pathological changes in blood chemistry, liver, and nephrology of the kidney. The GABA level estimation in the whole brain of mice was performed to predict the mechanistic study of the selected compounds. [ABSTRACT FROM AUTHOR]

Gamma-Aminobutyric Acid (GABA) inhibitory neurotransmitter departs an energetic role in brain signalling system. Levels of GABA in the brain influence human behaviour, diminishes in the degree of GABA can cause seizures, depression, Parkinson's. To put it plainly, it plays a basic part in the significant issues of mind. It is exceptionally important to cure the issues linked to GABA. Writing overview proposed that nipecotic acid is an intense GABA reuptake inhibitor. This scaffold is likewise present in one of the promoted anticonvulsant drugs 'Tiagabine'. Tiagabine is only drug in the market which works through this mechanism however the medication is regulated with one more prescription for the synergistic impact. Nipecotic acid has several disadvantages such as it can't cross the blood-brain barrier because of its hydrophilic and zwitterionic nature. To avoid this problem nipecotic acid scaffold hybrids with the different aromatic groups can enhance the physical (lipophilicity) as well as biological properties of the resultant compound. So, there is a dire requirement for compounds that work through this mechanism. Several medicinal chemists and researchers are already working in this field and developed outstanding newer molecules. This review article compiles these developed new hybrids along with design strategies, structure-activity relationship, and biological activity as well as in silico studies. This review also demonstrates the synthesis of nipecotic acid and the core mechanism through which nipecotic acid acts as a GABA reuptake inhibitor. [Display omitted] • Hybrids of Nipecotic acid emerged as potential drug candidates. • In recent years target selectivity is in great focus for the development of selective inhibitors. • The GABA reuptake inhibition of the synthesized potent derivatives was discussed along with their SAR. • The review focused on biological activity, SAR and in silico studies of developed GABA reuptake inhibitors. [ABSTRACT FROM AUTHOR]

Several generations of antiepileptic drugs (AEDs) are available in the market for the treatment of seizures, but these are amalgamated with acute to chronic side effects. The most common side effects of AEDs are dose-related, but some are idiosyncratic adverse drug reactions (ADRs) that transpire due to the formation of reactive metabolite (RM) after the bioactivation process. Because of the adverse reactions patients usually discontinue the medication in between the treatment. The AEDs such as valproic acid, lamotrigine, phenytoin etc., can be categorized under such types because they form the RM which may prevail with life-threatening adverse effects or immune-mediated reactions. Hepatotoxicity, teratogenicity, cutaneous hypersensitivity, dizziness, addiction, serum sickness reaction, renal calculi, metabolic acidosis are associated with the metabolites of drugs such as arene oxide, N -desmethyldiazepam, 2-(1-hydroxyethyl)-2-methylsuccinimide, 2-(sulphamoy1acetyl)-phenol, E−2-en-VPA and 4-en-VPA and carbamazepine-10,11-epoxide, etc. The major toxicities are associated with the moieties that are either capable of forming RM or the functional groups may itself be too reactive prior to the metabolism. These functional groups or fragment structures are typically known as structural alerts or toxicophores. Therefore, minimizing the bioactivation potential of lead structures in the early phases of drug discovery by a modification to low-risk drug molecules is a priority for the pharmaceutical companies. Additionally, excellent potency and pharmacokinetic (PK) behaviour help in ensuring that appropriate (low dose) candidate drugs progress into the development phase. The current review discusses about RMs in the anticonvulsant drugs along with their mechanism vis -a- vis research efforts that have been taken to minimize the toxic effects of AEDs therapy. [Display omitted] • Reactive metabolites of established antiepileptic drugs (AEDs) with their acute/chronic side-effects are reported. • Various synthetic strategies to minimize the toxicity under each category of AEDs are discussed. • Preclinical data for the synthesized derivatives is represented as compared to standard AEDs. • Structural activity relationship has been discussed for various synthesized derivatives. [ABSTRACT FROM AUTHOR]

[Display omitted] • Total 12 indole-3-subtituted pyrazoline and oxazole derivatives were synthesized. • These compounds were evaluated for in vivo and in vitro anti-inflammatory activity. • Compound 15c and 15f presented more promising and comprehensive NSAID-like profile. • Oxadiazole derivatives were found more potent than pyrazoline derivatives. There are several potential side and adverse effects are found to be associated with the anti-inflammatory drugs in clinical practice. The long-term use of these clinical agents highly unsafe. It encouraged the development of novel heterocyclic compounds with potential anti-inflammatory activity and low to no toxicity. In present investigation, a total of 12 indole functionalized pyrazole and oxadiazole derivatives were designed, synthesized and evaluated for the in-vivo anti-inflammatory and analgesic potential. These compounds displayed comparable anti-inflammatory and analgesic potential to the reference drugs. Finally, molecular docking analysis was performed considering different anti-inflammatory targets to determine the mechanistic target of the designed molecules. Detailed analysis suggested that the molecules inhibit COX-2, preferably over other anti-inflammatory targets. The results suggested that two compounds (15c and 15f) were found promising candidates for the development of novel anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

• Recent developments of nitrogen-containing heterocyclic compounds as antidepressant have been discussed. • The antidepressant profile of the potent derivatives along with structural insights is presented. • The SAR studies of recently developed compounds are discussed in details for providing key structural features. • The lead compounds for further development are identified and discussed in the perspective part of this review. According to the World Health Organization (WHO), depression is a common mental disorder and includes complex interaction between social and psychological behaviour affecting 264 million people worldwide. The review aims to highlight the role and importance of nitrogen-based heterocyclics in the development of antidepressant compounds. Many research groups have attempted to design drug candidates capable of binding within the receptors. The commonest drug design strategy includes the incorporation of different structural features widely recognized as an antidepressant in the synthesized derivatives to enhance their CNS antidepressant effects. In this review, we have shed light on nitrogenous heterocyclic moieties such as quinazoline, pyridine, pyrimidine, pyrrolidine, imidazole, pyrazole, piperidine, oxadiazole, benzimidazole, benzothiazole, piperazine, triazine, purine, benzoxazole, and isoxazole as core nucleus and/or in combination as an antidepressant compound. These molecules with different structural features were noted to exert their antidepressant effects by multiple mechanisms viz., selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase (MAO) inhibitors, and Catechol- O -methyltransferase (COMT) inhibitors. The review focuses on the selection of these heterocyclic moieties for the further design and development of promising antidepressants by taking a clue from the earlier reported potent antidepressant compounds or from the marketed products. The results have been correlated with their structural activity relationship (SAR) to identify the substituents for the potency and selectivity within the receptors. This review might help the researchers working in the antidepressant field to develop more novel molecules that could fill the gap by improving potency and reducing toxicity. [Display omitted] [ABSTRACT FROM AUTHOR]

• COVID-19 created an unprecedented medical and economic crisis all over the world. • Spike protein, RNA dependent RNA polymerase and Mpro Protease are major targets for COVID-19. • Similarity and key amino acid interactions of these are compared with SARS-CoV. • It will help to understand key amino acids essential for interactions at the active site of target proteins in SARS-CoV-2. SARS-CoV-2 (COVID-19) epidemic has created an unprecedented medical and economic crisis all over the world. SARS-CoV-2 is found to have more contagious character as compared to MERS-CoV and is spreading in a very fast manner all around the globe. It has affected over 31 million people all over the world till date. This virus shares around 80% of genome similarity with SARS-CoV. In this perspective, we have explored three major targets namely; SARS-CoV-2 spike (S) protein, RNA dependent RNA polymerase, and 3CL or Mpro Protease for the inhibition of SARS-CoV-2. These targets have attracted attention of the medicinal chemists working on computer-aided drug design in developing new small molecules that might inhibit these targets for combating COVID-19 disease. Moreover, we have compared the similarity of these target proteins with earlier reported coronavirus (SARS-CoV). We have observed that both the coronaviruses share around 80% similarity in their amino acid sequence. The key amino acid interactions which can play a crucial role in designing new small molecule inhibitors against COVID-19 have been reported in this perspective. Authors believe that this study will help the medicinal chemists to understand the key amino acids essential for interactions at the active site of target proteins in SARS-CoV-2, based on their similarity with earlier reported viruses. In this review, we have also described the lead molecules under various clinical trials for their efficacy against COVID-19. [ABSTRACT FROM AUTHOR]

Pyrazolines remain privileged heterocycles in drug discovery. 2-Pyrazoline scaffold has been proven as a ubiquitous motif which is present in a number of pharmacologically important drug molecules such as antipyrine, ramifenazone, ibipinabant, axitinib etc. They have been widely explored by the scientific community and are reported to possess wide spectrum of biological activities. For combating unprecedented diseases and worldwide increasing drug resistance, 2-pyrazoline has been tackled as a fascinating pharmacophore to generate new molecules with improved potency and lesser toxicity along with desired pharmacokinetic profile. This review aims to summarizes various recent advancements in the medicinal chemistry of pyrazoline based compounds with the following objectives: (1) To represent inclusive data on pyrazoline based marketed drugs as well as therapeutic candidates undergoing preclinical and clinical developments; (2) To discuss recent advances in the medicinal chemistry of pyrazoline derivatives with their numerous biological significances for the eradication of various diseases; (3) Summarizes structure-activity relationships (SAR) including in silico and mechanistic studies to afford ideas for the design and development of novel compounds with desired therapeutic implications. Image 1 • Pyrazoline is considered as an interesting scaffold with diverse array of pharmacological properties. • Recent advances in numerous therapeutic implications of pyrazoline derivatives have been described in this article. • The review provides a deep insight regarding in vitro and in vivo pharmacological activities of pyrazolines. • Their SAR, in silico and mechanistic studies has also been described in the manuscript. • The article provides enormous idea to explore therapeutic potentials of new pyrazoline motifs. [ABSTRACT FROM AUTHOR]

Most of the anti-inflammatory drugs in clinical practice are becoming outdated owing to their potential side and adverse effects. These are found to be highly unsafe for long term use. Thus, since last few years, new anti-inflammatory agents are being developed and number of them are in advanced stages of clinical trials. Heterocyclic molecules have gained great attention of chemists due to their similarity to different biological precursors. In the current review, we have highlighted the recent developments (2015 onwards) in designing and synthesis of various heterocyclic anti-inflammatory molecules along with detailed SAR studies. The principal objective of this review is to provide a profound overview of the recently explored heterocyclic anti-inflammatory agents belonging to various classes such as pyrazole, pyrimidine, benzimidazole, indole, and other related heterocyclic compounds. In addition, an enlarged view on potential interactions of synthetic preparations with target inflammatory enzymes or cytokines has been provided. We have also enlisted lead compounds undergoing different clinical trials against inflammation. The elementary aim of this review is to provide restructured knowledge regarding heterocyclic molecules which will be valuable for the scientists working in the field of anti-inflammatory chemistry. The authors believe that lead compounds mentioned in the report will help to design and develop novel anti-inflammatory drug molecules targeting various factors involved in the progression of inflammation. Image 1 • This review is focused on the recent developments in heterocyclic anti-inflammatory agents (2015 onwards). • Anti-inflammatory agents bearing different heterocyclic moieties are discussed. • The SAR of newly synthesized derivatives is explained for understanding designing strategies. • This review may help medicinal chemists to design and develop novel anti-inflammatory drug molecules. [ABSTRACT FROM AUTHOR]

• Three different series of new 1,5-benzodiazepines were synthesized. • All the compounds were screened in vivo to evaluate their CNS depressant and antiepileptic activity. • Compound 11b exhibited most potent CNS depressant activity whereas 10c displayed significant antiepileptic activity. • In silico studies were performed. Benzodiazepines (BZDs) represent a class of privilege scaffold in the modern era of medicinal chemistry as CNS active agents and BZD based drugs are used to treat different psychotic disorders. Inspired from the therapeutic potential of BZDs as promising CNS active agents, in the present work three different series of 1,5-benzodiazepines bearing various substitutions at position 2 and 4 of the benzodiazepine core were synthesized by condensing different substituted chalcones with o -phenylenediamine in the presence of piperidine as a base catalyst. Structural characterization of title compounds was done by using various analytical techniques such as IR, NMR, elemental analysis and mass spectral data. All the synthesized compounds (9a-d , 10a-e and 11a-c) were subjected to in vivo neuropharmacological studies to evaluate their CNS depressant and antiepileptic activity. Results of in vivo evaluation data showed that analogue 11b exhibited potent CNS depressant activity which was comparable to the standard drug diazepam. Compounds 10b and 10c displayed significant antiepileptic activity however they were less potent than the standard drug phenobarbitone. Molecular docking studies were performed using MOE software to find the interaction pattern and binding mode at the GABAA receptor (PDB Id: 6HUP). The results of the docking studies were in good agreement with the observed in vivo activity and revealed the satisfactory binding mode of the compounds within the binding site of the protein. The docking scores for the most promising candidates 10c , 11b and Diazepam were found to be −9.18, −9.46 and −9.88, respectively. Further, the compounds showed compliance with the Lipinski's 'rule of five' and exhibited favourable drug-likeness scores. The identified leads can be explored further for the design and development of new BZD based psychotropic agents. [ABSTRACT FROM AUTHOR]