[reaction: see text] A convergent method has been found to prepare 4-aza-2,3-didehydropodophyllotoxin and derivatives in a one-pot procedure. The mechanism of the reaction between tetronic acid, anilines, and benzaldehydes is discussed.

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The twelve new compounds were synthesized and studied for their antimicrobial activity. The compounds appeared to be promising antimicrobial agents and could be the lead compounds for new, more potent drugs. According to the docking prediction, the compounds could be MurB inhibitors.

Novel indolizine scaffolds as COX-2 inhibiting agents.

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 Mycobacterium tuberculosis (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. Indolizine 4 was identified as the most promising anti-mycobacterial agent, displaying minimum inhibitory concentration (MIC) values of 4 and 32 μg/mL against H37Rv and MDR strains, respectively. Furthermore, an in silico study was carried out for prospective molecular target identification and revealed favorable interactions with the target enzymes CYP 121, malate synthase, and DNA GyrB ATPase. None of the potent molecules presented toxicity against peripheral blood mononuclear (PBM) cell lines, demonstrating their potentiality to be used for drug-sensitive and drug-resistant tuberculosis therapy.

Background: Several promising compounds against multi-drug-resistant Mycobacterium tuberculosis (MTB) are currently in the drug discovery and development pipeline. While it has yet to establish candidature in this pipeline, early results have been promising for the putative anti-mycobacterial potency of the indolizine scaffold. Methods: The molecular properties, as well as the Absorption, Disruption, Metabolism, Excretion and Toxicity (ADMET) of indolizines were assessed using the Accelry's Discovery Studio 4.0 client package. Results: The current study evaluated the in vitro potency of 14 diversely substituted indolizine congeners against H37Rv and multi-drug-resistant strains of M. tuberculosis. While all 14 congeners showed potent anti-mycobacterial activity, only three of them had optimal drug-likeness and toxicology, as per in silico evaluations. Conclusion: The results of the current study identify three indolizine congeners (ethyl 2-methyl-3-(4-methylbenzoyl) indolizine-1-carboxylate (1b)), ethyl 7-acetyl-3-benzoyl-2-methylindolizine-1-carboxylate (3a) and ethyl 7-acetyl-3-benzoyl-2-ethylindolizine-1carboxylate (3b) with good anti-mycobacterial potency and acceptable drug-likeness and toxicity profiles. Furthermore, the study narrows down the list of indolizine congeners for further evaluation and underscores the importance of computational tools in mitigating the over-utilization of resources and associated costs of drug discovery.

: Over the past decades, a dramatically tremendous rise in invasive fungal infection diseases attributed to the yeast Candida albicans in immunocompromised individuals poses a serious challenging issue. Another alarming concern is the emergence of multi-drug resistant pathogens to the existing medicines due to their overuse and misuse. 25% to 55% mortality, caused by the invasive infection, was recently reported. Despite a large variety of drugs available to treating invasive candidiasis, only two of them containing a 1,2,4-triazole core, fluconazole and itraconazole, are efficient for the infection therapy induced by fungal Candida species. Moreover, the long-term therapy associated with the azole medications has led to an increase in azole resistance and to high risk of toxicity. Despite numerous outstanding achievements in antifungal drug discovery, the development of novel potent antifungal agents in view to develop more potent and safer fungicides and to overcome the resistance problem associated with the actual drugs is becoming the main focus point for medicinal chemists. Thus, the purpose of the present review is to outline the progresses of the last decade in medicinal chemistry research devoted to the 1,2,4-triazole-based derivatives as potential antifungal agents. The structure activity relationship of these compounds is also discussed.

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