Indole alkaloids represent a large subset of natural products, with more than 4100 known compounds. The majority of these alkaloids are biologically active, with some exhibiting excellent antitumor, antibacterial, antiviral, antifungal, and antiplasmodial activities. Consequently, the natural products of this class have attracted considerable attention as potential leads for novel therapeutics and are routinely isolated, characterized, and profiled to gauge their biological potential. However, data on indole alkaloids, their various structures, and bioactivities are complex due to their diverse sources, such as plants, fungi, bacteria, sponges, tunicates, and bryozoans; thus, isolation methods produce an incredible trove of information. The situation is exacerbated when synthetic derivatives, as well as their structures, bioactivities, and synthetic schemes, are considered. Thus, to make such data comprehensive and inform researchers about the current field’s state, this review summarizes recent reports on novel indole alkaloids. It deals with the isolation and characterization of 250 novel indole alkaloids, a reappraisal of previously reported compounds, and total syntheses of indole alkaloids. In addition, several syntheses and semi-syntheses of indole-containing derivatives and their bioactivities are reported between January 2019 and July 2022.

Folate grafted and thiolated chitosan was synthesized and wrapped on the surface of mixed phosphatidylcholine based nanoliposomes (NLs) to improve the oral absorption and targeted pharmacological activity of anti-cancer drugs against breast cancer. In this study, a chitosan derived thiomer, having intrinsic properties of P-glycoprotein (P-gp) efflux pump inhibition, mucoadhesion and controlled drug release at a target site, was exploited to improve the performance of docetaxel (DTX) loaded NLs for better oral pharmacokinetics, targeted anti-cancer activity, liposomal stability and the physical characteristics of NLs. Thiomer enveloped nanoliposomes (ENLs) and bare nanoliposomes (NLs) were synthesized with the ingredient ratio pre-determined via Response Surface Methodology (RSM) plots by Design Expert® software. ENLs and NLs were thoroughly characterized for their surface chemistry, particle size, zeta potential, PDI, encapsulation efficiency, stability and release profile. ENLs were spherical in shape with a particle size of 328.5 ± 30 nm, a positive zeta potential of 18.81 ± 2.45 and a high encapsulation efficiency of 83% for DTX. Controlled release of DTX from formulations was observed for over 72 h for each formulation. The presence of thiol groups at the surface of the ENLs resulted in higher swelling and in situ gelling properties compared to the corresponding NLs. Furthermore, ENL/mucin mixtures showed a time dependent increase in viscosity for up to 12 h, leading to a 19.07-fold increased viscosity. Ex vivo permeation and P-glycoprotein inhibiting properties, studied in rat's small intestine, showed a 9.6-fold higher permeation and 13-fold enhancement of DTX in the presence of ENLs. In vitro cytotoxicity studies indicated that the ENLs can efficiently kill MD-MB-231 breast cancer cells with 200 fold lower IC₅₀ values than DTX alone as a positive control. The pharmacokinetic study revealed that the ENLs significantly improved the oral bioavailability of DTX i.e. up to 13.6 fold as compared to an aqueous dispersion of DTX. Therefore, these enveloped hybrid nanoliposomes (ENLs) have the potential to be developed as useful nanocarriers for efficient oral delivery and breast cancer management using DTX.

Plant-mediated synthesis of ZnO Nanoparticles (NPs) have multiple advantages over conventional synthetic methods like easy, inexpensive, eco-friendly, nontoxic by-products and no critical conditions of temperature and pressure required. In this study, 9.1 g ZnO NPs were synthesized from 230 mL of 0.2 M Zinc acetate dihydrate and 100 mL of green tea leaves extract at room temperature (25°C). The leaves extract was prepared by heating 10gm dried leaves in 100 mL of deionized distilled water at 80°C for 2 h. The synthesized ZnO NPs were dried at 40°C for 24 h and calcined at 100°C for 1 h. The agar well diffusion method was used to evaluate ZnO NPs for antimicrobial activity of selected pathogenic strains. A clear zo“ne of inhibition was measured; 40.05 mm ± 0.137 for Staphylococcus aureus, 36.15 mm ± 0.304 for Escherichia coli and 40.10 mm ± 0.050 for Aspergillus niger that were comparably better results than standard antibiotic Gentamycin that showed 25 and 26 mm zone of inhibition for Staphylococcus aureus and Escherichia coli respectively. The minimum inhibitory concentration scored as 9.765µg ± 0.00, 9.531µg ± 0.00 and 5000µg ± 0.00 for Staphylococcus aureus, Escherichia Coli and Aspergillus niger respectively, was documented low concentration than reported so far concentrations of green tea ZnO NPs.

Fluorescent pseudomonads have been isolated from halophytes, mesophytes, and xerophytes of Pakistan. Among these, eight isolates, GS-1, GS-3, GS-4, GS-6, GS-7, FS-2 (cactus), ARS-38 (cotton), and RP-4 (para grass), showed antifungal activity and were selected for detailed study. Based on biochemical tests and 16S rRNA gene sequences, these were identified as strains of P. chlororaphis subsp. chlororaphis and aurantiaca. Secondary metabolites of these strains were analyzed by LC-MS. Phenazine-1-carboxylic acid (PCA), 2-hydroxy-phenazine, Cyclic Lipopeptide (white line-inducing principle (WLIP)), and lahorenoic acid A were detected in variable amounts in these strains. P. aurantiaca PB-St2 was used as a reference as it is known for the production of these compounds. The phzO and PCA genes were amplified to assure that production of these compounds is not an artifact. Indole acetic acid production was confirmed and quantified by HPLC. HCN and siderophore production by all strains was observed by plate assays. These strains did not solubilize phosphate, but five strains were positive for zinc solubilization. Wheat seedlings were inoculated with these strains to observe their effect on plant growth. P. aurantiaca strains PB-St2 and GS-6 and P. chlororaphis RP-4 significantly increased both root and shoot dry weights, as compared with uninoculated plants. However, P. aurantiaca strains FS-2 and ARS-38 significantly increased root and shoot dry weights, respectively. All strains except PB-St2 and ARS-38 significantly increased the root length. This is the first report of the isolation of P. aurantiaca from cotton and cactus, P. chlororaphis from para grass, WLIP and lahorenoic acid A production by P. chlororaphis, and zinc solubilization by P. chlororaphis and P. aurantiaca.