Identification of potent indolizine derivatives against Mycobacterial tuberculosis: In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies.

In the current study, two sets of compounds: (E)-1-(2-(4-substitutedphenyl)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium derivatives (3a-3e); and (E)-3-(substitutedbenzoyl)-7-((hydroxyimino)methyl)-2-substitutedindolizine-1-carboxylate derivatives (5a-5j), were synthesized and biologically evaluated against two strains of Mycobacterial tuberculosis (ATCC 25177) and multi-drug resistant (MDR) strains. Further, they were also tested in vitro against the mycobacterial InhA enzyme. The in vitro results showed excellent inhibitory activities against both MTB strains and compounds 5a-5j were found to be more potent, and their MIC values ranged from 5 to 16 μg/mL and 16-64 μg/mL against the M.

Oxime-functionalized anti-insecticide fabric reduces insecticide exposure through dermal and nasal routes, and prevents insecticide-induced neuromuscular-dysfunction and mortality.

Farmers from South Asian countries spray insecticides without protective gear, which leads to insecticide exposure through dermal and nasal routes. Acetylcholinesterase plays a crucial role in controlling neuromuscular function. Organophosphate and carbamate insecticides inhibit acetylcholinesterase, which leads to severe neuronal/cognitive dysfunction, breathing disorders, loss of endurance, and death.

Design, synthesis and characterization of ethyl 3-benzoyl-7-morpholinoindolizine-1-carboxylate as anti-tubercular agents: In silico screening for possible target identification.

A thorough search for the development of innovative drugs to treat tuberculosis, especially considering the urgent need to address developing drug resistance, we report here a synthetic series of ethyl 3-benzoyl-7-morpholinoindolizine-1-carboxylate analogues (5a-o) as potent anti-tubercular agents. These morpholino-indolizines were synthesized by reacting 4-morpholino pyridinium salts, with various electron-deficient acetylenes to afford the ethyl 3-benzoyl-7-morpholinoindolizine-1-carboxylate analogues (5a-o). All synthesized intermediate and final compounds are characterized by spectroscopic methods such as H NMR, C NMR and HRMS and further examined for their anti-tubercular activity against the M.

Synthesis, characterization, and anti-inflammatory properties of novel ethyl 3-benzoyl-7-(trifluoromethyl)indolizine-1-carboxylate derivatives: In silico and in vitro analysis.

Series of 7-(Trifluoromethyl) substituted indolizine 4a-g was synthesized using the one-pot method. Spectroscopic techniques such as IR, H-NMR, C-NMR, and HRMS were used for the structure confirmation of newly synthesized compounds. These 4a-g compounds were tested for their anti-inflammatory activity.

Synthesis, characterization and larvicidal studies of ethyl 3-benzoyl-7-(piperidin-1-yl)indolizine-1-carboxylate analogues against and cheminformatics approaches.

According to WHO, in 2021, there was an estimation of 247 million malaria cases from 84 malaria-endemic countries. Globally an estimated count of 2 billion malaria cases and 11.7 million deaths due to malaria were recorded in the past two decades.

Nucleophilic sulfur controlled efficient ketothioamide synthesis from tribromomethyl carbinols.

A mild, catalyst and oxidant-free efficient protocol for synthesizing α-ketothioamides is reported with a broad substrate scope. The presented protocol demonstrates the confined reactivity of amines. The polysulfide derived from elemental sulfur and amines in an aqueous medium drives the pathway toward diverse α-ketothioamides over thioamides.

Synthesis, biological evaluation, and computational investigation of ethyl 2,4,6-trisubstituted-1,4-dihydropyrimidine-5-carboxylates as potential larvicidal agents against .

Malaria is one of the most known vector-borne diseases caused by female mosquito bites. According to WHO, about 247 million cases of malaria and 619,000 deaths were estimated worldwide in 2021, of which 95% of the cases and 96% of deaths occurred in the African region. Sadly, about 80% of all malaria deaths were of children under five years old.

Development of as functional food targeting NRF2 signaling: antioxidant and anti-inflammatory activity in experimental model systems.

Pharmacological activation of nuclear factor erythroid 2 related factor 2 (NRF2) provides protection against several environmental diseases by inhibiting oxidative and inflammatory injury. Besides high in protein and minerals, leaves contain several bioactive compounds, predominantly isothiocyanate moringin and polyphenols, which are potent inducers of NRF2. Hence, leaves represent a valuable food source that could be developed as a functional food for targeting NRF2 signaling.

Mass spectrometry-based metabolomics approach and in vitro assays revealed promising role of 2,3-dihydroquinazolin-4(1H)-one derivatives against colorectal cancer cell lines.

Colorectal cancer (CRC) is the most frequent form of gastrointestinal cancer and one of the major causes of human mortality worldwide. Many of the current CRC therapies have limitations due to multidrug resistance and/or severe side effects. Quinazoline derivatives are promising lead compounds with a wide range of pharmacological actions.

Antitubercular, Cytotoxicity, and Computational Target Validation of Dihydroquinazolinone Derivatives.

A series of 2,3-dihydroquinazolin-4(1)-one derivatives (-) was screened for in vitro whole-cell antitubercular activity against the tubercular strain H37Rv and multidrug-resistant (MDR) (MTB) strains. Compounds and with di-substituted aryl moiety (halogens) attached to the 2-position of the scaffold showed a minimum inhibitory concentration (MIC) of 2 µg/mL against the MTB strain H37Rv. Compound with an imidazole ring at the 2-position of the dihydroquinazolin-4(1)-one also showed significant inhibitory action against both the susceptible strain H37Rv and MDR strains with MIC values of 4 and 16 µg/mL, respectively.

1,2,3-Triazolyl-tetrahydropyrimidine Conjugates as Potential Sterol Carrier Protein-2 Inhibitors: Larvicidal Activity against the Malaria Vector and In Silico Molecular Docking Study.

Alteration of insect growth regulators by the action of inhibitors is becoming an attractive strategy to combat disease-transmitting insects. In the present study, we investigated the larvicidal effect of 1,2,3-triazolyl-pyrimidinone derivatives against the larvae of the mosquito , a vector of malaria. All compounds demonstrated insecticidal activity against mosquito larvae in a dose-dependent fashion.

Anti-tubercular activity and molecular docking studies of indolizine derivatives targeting mycobacterial InhA enzyme.

A series of 1,2,3-trisubstituted indolizines (, and ) were screened for whole-cell anti-tubercular activity against the susceptible H37Rv and multidrug-resistant (MDR) (MTB) strains. Compounds , , and were active against the H37Rv-MTB strain with minimum inhibitory concentration (MIC) ranging from 4 to 32 µg/mL, whereas the indolizines with ethyl ester group at the 4-position of the benzoyl ring also exhibited anti-MDR-MTB activity (MIC = 16-64 µg/mL). docking study revealed the enoyl-acyl carrier protein reductase (InhA) and anthranilate phosphoribosyltransferase as potential molecular targets for the indolizines.

Crystallography, Molecular Modeling, and COX-2 Inhibition Studies on Indolizine Derivatives.

The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (-) were carried out and evaluated for COX-2 enzyme inhibition.

Investigation of Antifungal Properties of Synthetic Dimethyl-4-Bromo-1-(Substituted Benzoyl) Pyrrolo[1,2-a] Quinoline-2,3-Dicarboxylates Analogues: Molecular Docking Studies and Conceptual DFT-Based Chemical Reactivity Descriptors and Pharmacokinetics Evaluation.

, an opportunistic fungal pathogen, frequently colonizes immune-compromised patients and causes mild to severe systemic reactions. Only few antifungal drugs are currently in use for therapeutic treatment. However, evolution of a drug-resistant fungal pathogen is of major concern in the treatment of patients, hence the clinical need for novel drug design and development.

4-Aryl-1,4-Dihydropyridines as Potential Enoyl-Acyl Carrier Protein Reductase Inhibitors: Antitubercular Activity and Molecular Docking Study.

Background: Tuberculosis remains one of the most deadly infectious diseases worldwide due to the emergence of multi-drug resistance (MDR) and extensively drug resistance (XDR) strains of Mycobacterium tuberculosis (MTB).

Aims: Currently, available drugs are getting resistant and toxic. Hence, there is an urgent need for the development of potent molecules to treat tuberculosis.

Microbial Metabolite Urolithin B Inhibits Recombinant Human Monoamine Oxidase A Enzyme.

Urolithins are gut microbial metabolites derived from ellagitannins (ET) and ellagic acid (EA), and shown to exhibit anticancer, anti-inflammatory, anti-microbial, anti-glycative and anti-oxidant activities. Similarly, the parent molecules, ET and EA are reported for their neuroprotection and antidepressant activities. Due to the poor bioavailability of ET and EA, the in vivo functional activities cannot be attributed exclusively to these compounds.

Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies.

A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-]quinoline-3-carboxylates - and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-]quinoline-2,3-dicarboxylates - have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8-128 µg/mL against H37Rv.

Structural investigation of methyl 3-(4-fluoro-benzo-yl)-7-methyl-2-phenyl-indolizine-1-carboxyl-ate, an inhibitory drug towards .

The title compound, CHFNO, crystallizes in the monoclinic centrosymmetric space group and its mol-ecular conformation is stabilized C-H⋯O intra-molecular inter-actions. The supra-molecular network mainly comprises C-H⋯O, C-H⋯F and C-H⋯π inter-actions, which contribute towards the formation of the crystal structure. The different inter-molecular inter-actions have been further analysed Hirshfeld surface analysis and fingerprint plots.

In silico Design and Synthesis of Tetrahydropyrimidinones and Tetrahydropyrimidinethiones as Potential Thymidylate Kinase Inhibitors Exerting Anti-TB Activity Against .

Background And Purpose: Tuberculosis has been reported to be the worldwide leading cause of death resulting from a sole infectious agent. The emergence of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis has made the battle against the infection more difficult since most currently available therapeutic options are ineffective against these resistant strains. Therefore, novel molecules need to be developed to effectively treat tuberculosis disease.

Larvicidal Activities of 2-Aryl-2,3-Dihydroquinazolin -4-ones against Malaria Vector , In Silico ADMET Prediction and Molecular Target Investigation.

Malaria, affecting all continents, remains one of the life-threatening diseases introduced by parasites that are transmitted to humans through the bites of infected mosquitoes. Although insecticides are currently used to reduce malaria transmission, their safety concern for living systems, as well as the environment, is a growing problem. Therefore, the discovery of novel, less toxic, and environmentally safe molecules to effectively combat the control of these vectors is in high demand.

Anti-Tubercular Activity of Substituted 7-Methyl and 7-Formylindolizines and In Silico Study for Prospective Molecular Target Identification.

Novel series of diversely substituted indolizines were designed, synthesized, and evaluated for their in vitro anti-mycobacterial activity against H37Rv and multi-drug-resistant (MDR) strains of (MTB). Many compounds exhibited significant inhibitory activity against MTB H37Rv strains. Indolizines 2d, 2e, and 4 were also found to be active against MTB clinical isolates with multi-resistance to rifampicin and isoniazid.

Novel Series of Methyl 3-(Substituted Benzoyl)-7-Substituted-2-Phenylindolizine-1-Carboxylates as Promising Anti-Inflammatory Agents: Molecular Modeling Studies.

The cyclooxygenase-2 (COX-2) enzyme is considered to be an important target for developing novel anti-inflammatory agents. Selective COX-2 inhibitors offer the advantage of lower adverse effects that are commonly associated with non-selective COX inhibitors. In this work, a novel series of methyl 3-(substituted benzoyl)-7-substituted-2-phenylindolizine-1-carboxylates was synthesized and evaluated for COX-2 inhibitory activity.

Design, synthesis, and structural elucidation of novel NmeNANAS inhibitors for the treatment of meningococcal infection.

Neisseria meningitidis is the primary cause of bacterial meningitis in many parts of the world, with considerable mortality rates among neonates and adults. In Saudi Arabia, serious outbreaks of N. meningitidis affecting several hundreds of pilgrims attending Hajj in Makkah were recorded in the 2000-2001 season.

Computational, crystallographic studies, cytotoxicity and anti-tubercular activity of substituted 7-methoxy-indolizine analogues.

Indolizines are heteroaromatic compounds, and their synthetic analogues have reportedly showed promising pharmacological properties. In this study, a series of synthetic 7-methoxy-indolizine derivatives were synthesised, characterised and evaluated for in vitro whole-cell anti-tuberculosis (TB) screening against susceptible (H37Rv) and multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) using the resazurin microplate assay method. The cytotoxicity was evaluated using the MTT assay.