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.

The relentless rise in cancer incidence has sparked an urgent quest for a treatment. For centuries, natural product resources have been the bedrock of medicinal and pharmaceutical industries, capturing the interests of researchers to explore more on the potential of natural products to treat illnesses. Above all, β-carbolines derived from alkaloids are well-known for their various biological and pharmacological properties. In this work, we review the methodologies to synthesize 3,9-disubstituted β-carbolines framework through Pictet–Spengler, metal-catalysed cross-coupling, and multicomponent reactions. In addition, this study aims to investigate how the structural modifications affect their biological activities, with an emphasis on anticancer and antibacterial properties. Besides, the modifications at the C-3 and N-9 positions were evaluated for efficiency and selectivity towards 3,9-disubstituted β-carbolines. This article also highlighted the adaptability of 3,9-disubstituted β-carbolines scaffolds for further use in drug development.

The relentless rise in Plasmodium falciparum’s resistance to existing antimalarial drugs has sparked an urgent quest for novel therapeutic agents. For centuries, natural resources have been the bedrock of medicinal remedies, with β-carboline emerging as a beacon of hope in antimalarial research. In this study, we delve into the potential of hyrtiosulawesine derivatives as revolutionary antimalarial compounds, utilizing hyrtiosulawesine as the crucial scaffold. Employing a sophisticated amalgamation of molecular docking and ADME (absorption, distribution, metabolism and excretion) profiling, we meticulously screened an extensive library of hyrtiosulawesine’s derivatives against P. falciparum. Based on advanced computational techniques, the binding affinities and interaction profiles were assessed and culminating in the selection of the most promising candidates based on their exceptional binding interactions. Moreover, the comprehensive ADME analyses were performed to assess the pharmacokinetic properties of these derivatives, ensuring their suitability as drug candidates. The results showed that most of the analogues exhibited strong binding affinities (-7.2 to -9.8 kcal/mol) to the Plasmodium falciparum lactate dehydrogenase (pfLDH) protein, surpassing that of hyrtiosulawesine itself. Among these, compounds 2t and 1w demonstrated the strongest binding, likely due to hydrogen bonding with Arg171 and Asn197. ADME profiling revealed that all hyrtiosulawesine derivatives displayed favourable drug-likeness properties and adhered to the Lipinski Rule of 5 (Ro5) indicating their potential efficacy as antimalarial agents. This investigation provides a foundation for further in vitro and in vivo investigations paving the way for the development of effective treatments against malaria.

Polyisobutylene succinic anhydride (PIBSA) is an important intermediate for ashless dispersant additives used in lubricant formulations, where conversion and exo-selectivity strongly influence product performance. In this work, the thermal synthesis of PIBSA derived from highly reactive polyisobutylene (HR-PIB) 1300 and 2300 was systematically investigated using a full factorial experimental design to evaluate the effects of feed molar ratio, reaction temperature, and stirring rate on conversion and exo-PIBSA yield. Structural confirmation was performed using ¹H NMR spectroscopy, gel permeation chromatography (GPC), and saponification value analysis. HR-PIB 1300 achieved conversions of 60–94%, while HR-PIB 2300 achieved conversions of 75–88% under the investigated conditions. A clear molecular-weight-dependent trade-off between conversion and exo-selectivity was observed. For PIBSA 1300, higher temperatures increased conversion but reduced selectivity, resulting in exo-PIBSA yields of 24–56%. In contrast, PIBSA 2300 achieved yields of up to 71%, highlighting the importance of mixing and mass-transfer effects in higher-viscosity systems. These findings demonstrate that optimal thermal maleation conditions are strongly dependent on polymer molecular weight and provide mechanistic insight for future optimization of industrial PIBSA production.