The emerging and reemerging forms of fungal infections encountered in the course of allogeneic bone marrow transplantations, cancer therapy, and organ transplants have necessitated the discovery of antifungal compounds with enhanced efficacy and better compatibility. A very limited number of antifungal compounds are in practice against the various forms of topical and systemic fungal infections. The trends of new antifungals being introduced into the market have remained insignificant while resistance towards the introduced drug has apparently increased, specifically in patients undergoing long-term treatment. Considering the immense potential of natural microbial products for the isolation and screening of novel antibiotics for different pharmaceutical applications as an alternative source has remained largely unexplored. Endophytes are one such microbial community that resides inside all plants without showing any symptoms with the promise of producing diverse bioactive molecules and novel metabolites which have application in medicine, agriculture, and industrial set ups. This review substantially covers the antifungal compounds, including volatile organic compounds, isolated from fungal endophytes of medicinal plants during 2013–2018. Some of the methods for the activation of silent biosynthetic genes are also covered. As such, the compounds described here possess diverse configurations which can be a step towards the development of new antifungal agents directly or precursor molecules after the required modification.
An efficient L-proline catalyzed one-pot synthesis of 3-amino-alkylated indoles has been developed via a three-component Mannich-type reaction viz.secondary amines, aldehyde and indoles under solvent-free conditions at room temperature. Several amino acids (acidic, basic and neutral) have been screened for the reaction but the best results were obtained with L-proline.
1 September 2017 in Bioorganic & Medicinal Chemistry Letters
Keeping in view various pharmacological attributes of indole and coumarin derivatives, a new series of indolindione–coumarin molecular hybrids was rationally designed and synthesized. All synthesized hybrid molecules were evaluated for their antimicrobial potential against Gram-negative bacterial strains (Escherichia coli and Salmonella enterica), Gram-positive bacterial strains (Staphylococcus aureus and Mycobacterium smegmatis), and four fungal strains (Candida albicans, Alternaria mali, Penicillium sp., and Fusarium oxysporum) by using the agar gel diffusion method. Among all synthetics, compounds K-1 and K-2 were found to be the best antimicrobial agents with the minimum inhibitory concentration values of 30 and 312 μg/mL, against Penicillium sp. and S. aureus, respectively. The biological data revealed some interesting facts about the structure–activity relationship which state that the electronic environment on the indolinedione moiety and carbon chain length between indolinedione and triazole moieties considerably affect the antimicrobial potential of the synthesized hybrids. Various types of binding interactions of K-2 within the active site of S. aureus dihydrofolate reductase were also streamlined by molecular modeling studies, which revealed the possible mechanism for potent antibacterial activity of the compound.