Indole-containing alkaloids are widely distributed in nature, and a variety of indole-containing alkaloids have already been applied in clinical practice. This review gives an overview of the advances in the development of indole alkaloids with antibacterial potential in the recent 10 years.

Indole/isatin-containing hybrids show promising activity against many clinically important Gram-positive and Gram-negative bacteria and are thus privileged scaffolds for the discovery of novel antibacterial candidates. This review, covering articles published between January 2015 and May 2020, summarizes the recent advances in the development of indole/isatin-containing hybrids as potential antibacterial agents.

Bis-ethyl 2-(2-cyanoacrylamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate derivatives 5–10 with aliphatic linkers were synthesized and tested in vitro as anticancer agents against HepG2, MCF-7, HCT-116, and BJ1 cells. Compounds 7 and 9 emerged as the most promising compounds, with IC₅₀ values (HepG2) of 13.5 and 32.2 µg/ml, respectively, compared with doxorubicin. The effects of compounds 7 and 9 on gene expression and DNA fragmentation were evaluated.

Novel hybrids of imidazopyridine and thiazolidinone ring compounds were synthesized as potent anticancer agents. The lead molecule was identified as N-[2-(4-hydroxyphenyl)-4-oxothiazolidin-3-yl]-4-(3H-imidazo[4,5-b]pyridin-2-yl)-4-oxobutanamide, showing an excellent spectrum of anticancer activities against breast, lung, and human prostate cancer cell lines (MCF-7, A549, and DU145).

PAK4 (p21-activated kinase 4) is associated with cancer, and the combined application of PAK4 and PD-1 inhibitors provides a new approach to avoid the resistance to PD-1 blockade therapy. In this paper, a structure-based drug design strategy was used to create a novel series of 2,4-diaminopyrimidine skeleton PAK4 inhibitors. Among these new derivatives, compound B6 can serve as a candidate for the development of a PAK4 inhibitor molecule.

A novel series of 1,3,4-thiadiazole derivatives was designed and synthesized as possible nontoxic, nonulcerogenic analgesic, and anti-inflammatory agents through COX-2 inhibition. The anti-inflammatory and analgesic activity of low-dose radiotherapy, in particular with a single dose of 0.5 Gy, was tested alone and in combination with the most potent compounds.

In this study, benzyl-1,2,3-triazole-linked 5-benzylidene (thio)barbiturate derivatives 7a–d and 8a–h were designed as potential tyrosinase inhibitors and free-radical scavengers. The thiobarbiturate derivative 8h and the barbiturate derivative 8b bearing 4-fluoro and 4-bromo groups on the benzyl–triazole moiety are the most potent tyrosinase inhibitors (IC₅₀s = 24.6 ± 0.9 and 26.8 ± 0.8 μM, respectively). Both compounds 8b and 8h are well accommodated in the active site of tyrosinase.

A series of novel coumarin–1,2,3-triazole-acetamide hybrids was tested for their inhibitory activity against metabolic enzymes such as α-glycosidase, α-amylase, acetylcholinesterase, butyrylcholinesterase, and human carbonic anhydrases I and II. The new hybrids represent potential drug candidates to treat diseases such as epilepsy, glaucoma, type-2 diabetes mellitus, Alzheimer's disease, and leukemia.

Novel tacrine analogs with lower toxicity were designed and synthesized. They could efficiently inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with IC₅₀ values of 1.55 and 0.23 µM, respectively. The most potent compounds (5e and 5d) could inhibit AChE-induced and self-induced amyloid-beta aggregation

Iridoids from Allamanda polyantha seed extract were isolated and evaluated for their in vitro antifungal activity. Plumieride and plumieridine were observed to cause alterations in Cryptococcus spp. cells, showing promising results as an antifungal agent.

Five dihydroxycoumarins were synthesized and investigated for their antioxidant and in vitro 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitory effects. The quantum-chemical properties of the coumarin derivatives were explored and molecular docking was performed to determine the binding strength of each coumarin derivative. Compound IV displayed the highest HMG-CoA reductase inhibitory activity, with IC₅₀ = 42.0 µM.

Prolonged maceration was compared with short-time pressurized microwave-assisted extraction (PMAE) at low temperatures. Low-temperature PMAE can attain reasonable extraction efficiencies with the added value of sparing compounds of low thermal stability. The method can also enable the recovery of compounds distinct from those obtained by maceration.