Nitrogen-containing heterocycles as important scaffold for selective and potent HDAC8 inhibition: a step towards effective, non-toxic and selective HDAC8 inhibitor discovery.

Selective inhibition of histone deacetylase 8 (HDAC8) has emerged as a promising approach for treating various diseases, including cancer. However, finding key structural features for HDAC8 inhibition and developing effective and selective HDAC8 inhibitors (HDAC8s) pose significant challenges. In the past few years, the development of various scaffolds for inhibiting HDAC8 has significantly risen and the quest continues.

Tautomeric Conflicts in Forty Small-Molecule Databases.

We have analyzed 40 different databases ranging in size from a few thousand to nearly 100 million molecules, comprising a total of over 210 million structures, for their tautomeric conflicts. A tautomeric conflict is defined as an occurrence of two or more structures within a data set identified by the tautomeric rules applied as being tautomers of each other. We tested a total of 119 detailed tautomeric transform rules expressed as SMIRKS, out of which 79 yielded at least one conflict.

Indigenous wisdom of a Kwatha to treat NASH: An insight into the mechanism.

Ethnopharmacological Relevance: Nonalcoholic fatty liver disease (NAFLD) is the most common severe liver disease globally, progressing further into nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Vasaguduchyadi Kwatha (VK) is an Ayurvedic formulation traditionally used to treat liver diseases and other metabolic complications. This study is an ethnopharmacological approach to unravel this indigenous remedy.

Network pharmacology and bioinformatics based investigation of : herb-drug interaction study.

(PF), a plant from the Euphorbiaceae family, is used extensively in ayurvedic formulations for its significant medicinal properties. When PF is administered alongside conventional drugs, there could be potential herb-drug interactions between the active compounds and the genes involved in drug transport and metabolism. Hence, this study was designed to investigate potential herb-drug interactions, focusing on elucidating their functional and pharmacological mechanisms, using an integrated approach of metabolite profiling and network pharmacology.

Antiviral Activity of Cinchona officinalis, a Homeopathic Medicine, against COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies have shown that hydroxychloroquine (HCQ) significantly inhibits SARS-CoV-2 infections .

Objective: Since the phytoconstituents of (CO) are similar to those of HCQ, the objective of this study was to test the antiviral potential of different homeopathic formulations of CO.

Metal-free synthesis of selenoesters directly from carboxylic acids using bifunctional selenoureas under batch and continuous-flow conditions.

A new metal-free method for the synthesis of selenoesters directly from carboxylic acids in a flow reactor is reported. The carboxylic acids, Michael acceptors, and bifunctional selenoureas (source of selenium and nucleophile, activator of carbonyl group) were reacted to obtain selenoesters (up to 70% yield). An evidence-backed plausible mechanism is also presented.

An update on ATP synthase inhibitors: A unique target for drug development in M. tuberculosis.

ATP synthase is a key protein in the oxidative phosphorylation process, as it aids in the effective production of ATP (Adenosine triphosphate) in all life's of kingdoms. ATP synthases have distinctive properties that contribute to efficient ATP synthesis. The ATP synthase of mycobacterium is of special relevance since it has been identified as a target for potential anti-TB molecules, especially Bedaquiline (BDQ).

Neuroprotective Effect of Methanolic Ajwa Seed Extract on Lipopolysaccharide-Induced Memory Dysfunction and Neuroinflammation: In Vivo, Molecular Docking and Dynamics Studies.

Islamic literature has indicated that daily consumption of Ajwa dates heals a variety of chronic diseases and disorders. The current research investigates the neuroprotective effect of methanolic Ajwa seed extract (MASE) on lipopolysaccharide (LPS)-induced cognitive deficits using multiple approaches. For animal studies, MASE (200 and 400 mg/kg, p.

Importance of tautomerism in drugs.

Tautomerism is an important phenomenon exhibited by many drugs. As we discuss in this review, identifying the different tautomers of drugs and exploring their importance in the mechanisms of drug action are integral components of current drug discovery. Nuclear magnetic resonance (NMR), infrared (IR), ultraviolet (UV), Raman, and terahertz spectroscopic techniques, as well as X-ray diffraction, are useful for exploring drug tautomerism.

Isolation of phytochemicals from followed by semisynthetic modification of ixoside via azomethine ylide cycloaddition; computational approach towards chemo-selection.

Aims of the study were the phytochemical investigation and chemical transformation of isolated compounds of medicinal plant listed in 'Ayurveda' like , endemic to Indian subcontinents. From chloroform extract of four compounds; Ursolic acid (), Maslinic acid (), Lupeol (), -sitosterol () and from methanol extract five compounds; -sitosterol-3---D-glucopyranoside (), 10----Methoxycinnamoylcatalpol (), Kaempferol-3---D-glucopyranoside (), 6--[6"()-hydroxy-2",6"dimethyl-2"(E)-7"-octadienoyl] catalpol () and Ixoside () were isolated. Ixoside was used for the semi-synthetic modification via azomethine ylide cycloaddition leading to novel spiro-oxindolo-pyrrolizidine adduct.

Targeting the cytochrome bc complex for drug development in M. tuberculosis: review.

The terminal oxidases of the oxidative phosphorylation pathway play a significant role in the survival and growth of M. tuberculosis, targeting these components lead to inhibition of M. tuberculosis.

Toward a Comprehensive Treatment of Tautomerism in Chemoinformatics Including in InChI V2.

We have collected 86 different transforms of tautomeric interconversions. Out of those, 54 are for prototropic (non-ring-chain) tautomerism, 21 for ring-chain tautomerism, and 11 for valence tautomerism. The majority of these rules have been extracted from experimental literature.

Tautomer Database: A Comprehensive Resource for Tautomerism Analyses.

We report a database of tautomeric structures that contains 2819 tautomeric tuples extracted from 171 publications. Each tautomeric entry has been annotated with experimental conditions reported in the respective publication, plus bibliographic details, structural identifiers (e.g.

Palladium-catalyzed arylation of 2H-chromene: a new entry to pyrano[2,3-c]carbazoles.

Pyrano[2,3-c]carbazoles which are biologically valuable and synthetically challenging frameworks are synthesized in high yields over five steps from commercially available resorcinol. Palladium-catalyzed arylation remains a key step in this novel strategy. The versatility of this protocol has been demonstrated by the synthesis of naturally occurring alkaloid clauraila C and 7-methoxyglycomaurin.

Investigation of anion-π interactions involving thiophene walls incorporated calix[4]pyrroles.

Thiophene containing "two-wall" aryl extended calix[4]pyrroles were synthesized for the first time, through acid catalyzed condensation of 2-acetylthiophenes with pyrrole. Isomeric "two-walled" calix[4]pyrroles (8a-10a and 8b-10b) were obtained in satisfactory yields and their halide anion binding strengths were investigated in the solution phase by (1)H NMR and in the gas phase by computational methods and mass spectrometry. Change in the chemical shifts of thiophene -CH-protons during the course of NMR titrations entailed participation of the thiophene rings in anion binding; this fact was further substantiated by computational methods.

Cu-catalyzed arylation of the amino group in the indazole ring: regioselective synthesis of pyrazolo-carbazoles.

Cu(II)-catalyzed cross-coupling of various aryl boronic acids with 5 and 6-amino indazoles has resulted in (arylamino)-indazoles. These (arylamino)-indazoles have been utilized in synthesizing medicinally important pyrazole-fused carbazoles via Pd(II)-catalyzed cross-dehydrogenative coupling (CDC). This combined N-arylation/C-H arylation strategy has been successfully applied to the regioselective synthesis of polyheterocycles 3,6-dihydropyrazolo[3,4-c]carbazoles and 1,6-dihydro pyrazolo[4,3-c]carbazoles.

DFT study on the oxygen transfer mechanism in nitroethenediamine based H2-receptor antagonists using the bis-dithiolene complex as the model catalyst for N-oxide reductase enzyme.

Nitroethenediamine is an important functional unit, which is present in H2-receptor antagonists. These drugs show low bioavailability due to the bacterial degradation caused by the N-oxide reductase type of enzymes present in the human colon. Quantum chemical studies have been carried out to elucidate the mechanism of metabolic degradation of nitroethenediamine in the active site of N-oxide reductase.

On the stability of zwitterions of pyridine sulfonylureas: the effect of isosterism, acidity, and microsolvation.

Pyridine sulfonylureas (PSUs) are known to exist in zwitterionic form in the solid phase. For example, torsemide, a diuretic drug, exists in three polymorphic forms: two of them in the zwitterionic state and one in the "partial zwitterionic" state. Initial computational analysis showed that the energy difference between the canonical and the zwitterionic states of a model PSU is very large in the gas phase (∼15 kcal/mol), thus disfavoring the zwitterionic state.

Site-selective electrophilic cyclization and subsequent ring-opening: a synthetic route to pyrrolo[1,2-a]quinolines and indolizines.

An efficient strategy for the synthesis of pyrrolo[1,2-a]quinolines and indolizines from pyranoquinolines via site-selective electrophilic cyclization and subsequent opening of pyran ring using silver/iodine under mild reaction conditions is described. This approach involves the preferential attack of the pyridyl nitrogen over aryl ring and leads to the formation of 5-endo-dig cyclized products. Quantum chemical calculations between C-N (ΔE(a) = 9.

Exploring the binding of HIV-1 integrase inhibitors by comparative residue interaction analysis (CoRIA).

Since the recognition of HIV-1 integrase as a novel and rational target for HIV therapeutics, remarkable progress has been made in the development of integrase inhibitors. Computational techniques have played a critical role in accelerating research in this area. However, most previous computational studies were based solely on ligand information.