Indole represents one of the most important privileged scaffolds in drug discovery. Indole derivatives have the unique property of mimicking the structure of peptides and to bind reversibly to enzymes, which provide tremendous opportunities to discover novel drugs with different modes of action. There are seven indole-containing commercial drugs in the Top-200 Best Selling Drugs by US Retail Sales in 2012. There are also an amazing number of approved indole-containing drugs in the market as well as compounds currently going through different clinical phases or registration statuses. This review focused on the recent development of indole derivatives as antiviral agents with the following objectives: 1) To present one of the most comprehensive listings of indole antiviral agents, drugs on market or compounds in clinical trials; 2) To focus on recent developments of indole compounds (including natural products) and their antiviral activities, summarize the structure property, hoping to inspire new and even more creative approaches; 3) To offer perspectives on how indole scaffolds as a privileged structure might be exploited in the future.

1-Acetyl-3,-5-diarylpyrazolines have received considerable interests from the fields of medicinal and agricultural chemistry due to their broad spectrum of biological activities. To discover new lead compounds exhibiting both fungicidal and insecticidal activities, a series of pyrazoline derivatives were designed and synthesized by introducing the beta-methoxyacrylate pharmacophore into the scaffold of 1-acetyl-3,5-diarylpyrazoline. The fungicidal activities against Pseudoperoniospora cubensis, Sphaerotheca fuliginea, Botrytis cinerea, and Rhizoctonia solani and the insecticidal activities against Aphis medicagini, Nilaparvata legen, Mythima separata, and Tetranychus cinnabarnus were screened. The most potent compound 13, 1-aceto-3-[m-[o-(E-1-methoxycarboxyl-2-methoxy)-1-yl]benzyloxy]phenyl-5-(benzo-[1,3]-dioxolyl)-4,5-dihydro- pyrazoline, was identified. Its fungicidal IC(50) values against P. cubensis and S. fuliginea are 26.6 and 57.6 microg mL(-1), respectively, while its insecticidal LC(50) value against M. separata is 26.6 microg mL(-1). These results indicated that compound 13 could be used as a lead for further developing new pyrazoline type products exhibiting both fungicidal and insecticidal activities.

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Streptochlorin is a kind of indole alkaloid derived from marine microorganisms. It is a promising lead compound due to its potent bioactivity in preventing many phytopathogens, as shown in our previous study. To explore the potential applications of this natural product, a series of novel benzoxaborole-containing streptochlorin derivatives were designed and synthesized through a one-step and catalyst-free reaction in water at room temperature. All target compounds were first screened for their antifungal profiles in vitro against six common phytopathogenic fungi. The results of bioassay revealed that most of the designed compounds exhibited more significant antifungal activities against Botrytis cinrea, Gibberella zeae, Rhizoctorzia solani, Colletotrichum lagenarium, and alternaria leaf spot under the concentration of 50 μg/mL, and this is highlighted by compounds 4i and 5f, which demonstrated impressive antifungal effects against G. zeae and R. solani, with their corresponding EC50 values 0.2983 and 0.2657 μg/mL, which are obviously better than positive control flutriafol and boscalid (5.2606 and 1.2048 μg/mL, respectively). Scanning electron microscopy on the hyphae morphology showed that compound 5b might cause mycelial abnormalities of G. zeae. 3D-QSAR studies of CoMFA and CoMSIA were carried out on 29 target compounds with antifungal activity against B. cinrea. The analysis results indicated that introducing appropriate electronegative groups at the 5-position of benzoxaborole and the 4,5-positions of the indole ring could effectively improve the anti-B. cinrea activity. Moreover, compound 5b showed good antifungal activities in vivo against Phytophthora capsici. Molecular docking was further explored to ascertain the practical value of the active compound as a potential inhibitor of LeuRS. The abovementioned results indicate that the designed benzoxaborole-containing streptochlorin derivatives could be further studied as template molecules of novel antifungal agents.

Herein, a divergent synthesis of a variety of 2α‐ and 5α‐substituted furan derivatives from 2‐hydroxy‐1,4‐diones is reported. By using appropriate substrates and an acid catalyst, the reactions occurred selectively through cyclization/1,6‐conjugate addition or cyclization/Friedel–Crafts‐type cascade reactions. A broad range of nucleophilic reagents (>10 types for the 1,6‐conjugate addition for 5α substitution and >20 types for the Friedel–Crafts‐type cascade reaction for 2α substitution), including alcohols, amides, furan, thiophene, pyrrole, indole, phenols, and many others, can successfully participate in the reactions, providing a universal strategy for a diversity‐oriented synthesis of α‐substituted furan derivatives. Deuteriation experiments and DFT calculations were carried out to support the proposed reaction mechanisms. Antifungal activity experiments revealed that products with an indole or 4‐hydroxycoumarin core substituted at the 2α position showed moderate activities against Rhizoctorzia solani and Botrytis cinerea, respectively.

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