Widespread resistance of Plasmodium falciparum to current artemisinin-based combination therapies necessitate the discovery of new medicines. Pharmacophoric hybridization has become an alternative for drug resistance that lowers the risk of drug–drug adverse interactions. In this study, we synthesized a new series of hybrids by covalently linking the scaffolds of pyrano[2,3-c]pyrazole with 4-aminoquinoline via an ethyl linker. All synthesized hybrid molecules were evaluated through in vitro screenings against chloroquine-resistant (K1) and -sensitive (3D7) P. falciparum strains, respectively. Data from in vitro assessments showed that hybrid 4b displayed significant antiplasmodial activities against the 3D7 strain (EC₅₀ = 0.0130 ± 0.0002 μM) and the K1 strain (EC₅₀ = 0.02 ± 0.01 μM), with low cytotoxic effect against Vero mammalian cells. The high selectivity index value on the 3D7 strain (SI > 1000) and the K1 strain (SI > 800) and the low resistance index value from compound 4b suggested that the pharmacological effects of this compound were due to selective inhibition on the 3D7 and K1 strains. Molecular docking analysis also showed that 4b recorded the highest binding energy on P. falciparum lactate dehydrogenase. Thus, P. falciparum lactate dehydrogenase is considered a potential molecular target for the synthesized compound.

β-Carboline bearing indole is one of the heterocyclic compounds that play a vital role in medicinal chemistry with various pharmacological effects such as anticancer, anti-acetylcholinesterase, anti-inflammation, antimalarial, antibacterial, anti-diabetic, and antioxidant. Over the last two decades, many studies on the synthesis and biological activity of indole β-carboline compounds have been conducted yet there is no appropriate data summary has been presented. Thus, the goal of this review was to highlight the synthesis pathway and bioactivity of substituted indole β-carboline reported from 2005 to date. In addition, this will encourage further investigation into the synthesis and evaluation of new indole β-carboline, in the hope of contributing to the development of potentially new medications for the treatment of various ailments.

A tridentate nitrogen-oxygen-sulfur (NOS) S-benzyl(2-oxoindolin-3-ylidene)dithiocarbazate, HSBISA (HL1) ligand was synthesized via a condensation reaction between S-benzylditihocarbazate (SBDTC) and isatin. The produced ligand was reacted with nickel(II) acetate salt in 1:2 (metal:ligand) ratio to yield a brown Ni(SBISA)2 complex (2) (SBISA = monoanionic form of HL1). Characterization of HL1 and its Ni(II) complex was performed via elemental analysis, FT-IR, ICP-AES, UV-Vis spectroscopy and mass spectrometry, along with molar conductivity and magnetic susceptibility measurement. Slow evaporation of 2 from DMSO at room temperature led to a structure crystallizing in the monoclinic P21/a space group with a = 18.6860(3), b = 11.3037(2), c = 19.8993(3), b = 112.1897(10), V = 3891.86(11) Å3, wR2 (all data) = 0.0407 and R1 = 0.0386 for data with I > 2σ(I). The nickel(II) metal center is ligated by doubly-deprotonated NOS monoanionic tridentate HL1 ligands forming a neural distorted octahedral Ni(SBISA)2×2DMSO (2a) complex. The antimicrobial assays of both compounds were performed on selected pathogenic bacteria and fungi strains. HIGHLIGHTS Octahedral Ni(II) complex was synthesized using acetate salt Compound was characterized via physico-chemical analyses Structural studies were resolved via single crystal X-ray diffraction Compound 2a crystallized in a monoclinic system (P21/a space group) with cell parameters a = 18.6860 (3), b = 11.3037 (2), c = 19.8993(3), b = 112.1897 (10), V = 3891.86 (11) Å3, wR2 (all data) = 0.0407 and R1 = 0.0386 for data with I > 2σ(I) Compound was evaluated for its antimicrobial activity GRAPHICAL ABSTRACT

The synthesis of diastereoisomers via diastereoselective hydrogenation of unreactive endocyclic enamine system of ethyl 4-hydrazinyl- and 4-(2-hydroxyethylamino)-5-oxo-2,5-dihydro-1H-pyrrole-3-carboxylates using palladium-based catalyst was developed. The steric and electronic properties of substituents, especially of the C² substituent, influenced both the yield and diastereoselectivity. Despite the reaction generated three chiral centers, the reduced compounds had either cis–trans or all-trans configuration which was successfully determined by means of 1D and 2D NMR experiments.