Current Bioactive Compounds - Volume 20, Issue 3, 2024

Background: The rising interest in natural pigments as alternatives is a result of the expanding usage of synthetic colorants and the negative consequences that go along with them. Noble natural pigments with higher stability and productivity are becoming popular in the food industry, and their diverse biological characteristics make them valuable for pharmaceutical applications. Microbes, especially gram-negative and positive bacteria, are considered attractive sources for replacing synthetic dyes. Prodigiosin, a tripyrrole red pigment produced as secondary metabolites by these bacteria, exhibits unusual properties and has potential as an effective proapoptotic agent against cancer and multi-drug resistant cells. Objective: This review aims to highlight the characteristics of prodigiosin and explore its potential applications as a therapeutic drug. Results: The review investigates the biosynthetic cluster genes of prodigiosin identified using the EZ-Tn5 transposon approach in different bacteria, including the pig gene cluster in Serratia sp., red gene cluster in S. coelicolor, and hap gene cluster in Hahella chejuensis. It is also described compound nature for producing host survival physiology. Prodigiosin has a common pyrrolylpyrromethane structure and is a member of the tripyrrole family. Numerous tri-pyrrole derivatives have been used in antibiotics and have demonstrated promise as pro-apoptotic agents against cancer and drug-resistant cells. Conclusion: Prodigiosin is an intriguing subject for investigating biosynthesis and exploitation through biotechnological methods due to its distinctive properties and potential as a medicinal medication. Future investigation and bioengineering on producing strains may synthesize functional derivatives with diverse applications.

Background: Amongst gene delivery vehicles, peptide-based vectors have drawn the intensive attraction of experts globally due to their simplicity and many advantages due to ease in design, biocompatibility, and safety. Rationally designed peptides are capable of condensing DNA molecules efficiently and facilitating gene expression in the target cells. Objective: This study aims to design, synthesize and evaluate short cationic peptides composed of several positively charges amino acids of lysine (K) and arginine (R) for gene delivery vehicle candidates. Methods: The short cationic peptides of PKKKRKV (P1), CHSPKKKRKV (P2), and YGRKKRRQRRR (P3) were synthesized using a solid-phase method on 2-chlorotrityl chloride resin. The crude peptides were purified using RP-HPLC and characterized by HR-TOF-ESI-MS and ¹H-NMR. The capability of the peptides to condense DNA was evaluated by ethidium bromide exclusion assay. Cytotoxicity study of the peptides was carried out in HEK-293T, CHO-K1, and HepG2 cells using MTT assay. Gene expression facilitated by the peptides was determined in the HEK-293T. Results: The peptides were successfully synthesized with high purity (> 90%) and in a high consistency with the synthetic products, as shown by the spectroscopic data. Physicochemical and biological evaluation showed that the cationic peptides are capable of condensing DNA molecule and have low cytotoxicity to the cells of HEK-293T, CHO-K1, and HepG2. Moreover, the cationic peptides facilitated gene delivery of green fluorescence protein more efficiently compared to PLL. Conclusion: The short cationic peptides rich in lysine and arginine have been successfully synthesized using solid-phase peptide synthesis method. They were found to be capable of condensing DNA, have low cytotoxicity, and facilitate gene delivery. However, structure modification or formulation of cationic peptide with lipid components to form cationic liposome is still needed to enhance transgene expression by these peptides.

Background: Cancer is the second leading cause of death globally and is responsible for 10 million deaths in 2020 (2.26 million breast cancer deaths). Due to the problems like drug resistance, toxicities and economic burden, there is a need for the development of novel anticancer agents. Objectives: To design novel flavone derivatives by 2D QSAR studies and docking studies and to evaluate the compounds as potential anticancer agents against MCF7 cell line by MTT assay. Methods: We designed a series of novel flavone derivatives by 2D QSAR modelling using the software QSARINS.The molecular docking studies were carried out to study the molecular interaction and binding affinitiesof the designed compounds against tyrosine protein kinase (PDB ID: 2SRC) by Auto DockVina software. ADMET profiles were calculated for all the designed compounds and five compounds were chosen for synthesis. The synthesized compounds were characterized and evaluated in-vitro for anticancer activity against MCF7 cell line by MTT assay. Based on 2D QSAR and molecular docking studies, compounds 3c, 3f, 3i and 3m were synthesized and evaluated for anticancer activity against MCF-7 cell lines. Results: Molecular docking studies of the compounds showed good binding affinity against tyrosine- protein kinase (2SRC). The synthesized flavone derivatives were evaluated for anti-cancer activity against human breast cancer cell line MCF-7 by MTT assay using cisplatin as a positive control. The novel flavone derivative (3c) exhibits more cytotoxicity effect, and the IC50 value of the compound was found to be 52.03 μg/ml. Optimization of these novel scaffolds requires extensive studies on more derivatives. Conclusion: The novel flavone derivatives will be good lead compounds targeting breast cancer.

Background: Adhatoda beddomei (Adosa), a kind of softwood, evergreen, perennial shrub, has been used as a source of endophyte bacteria. Adhatoda beddomei has a wide variety of chemicals, including anthocyanins, aminophylline, alkaloids, cardiac glycosides, isoprenaline, triterpenoids, resins, flavonoids, tannins, sterol, saponins, etc. The root, stem, and leaf parts of Adathoda beddomei are most often used in indigenous medicine. Moreover, the root bark is also used to cure several conditions, including leprosy, fever, and bleeding. Objective: Some important bioactive metabolites were obtained from endophytes bacteria and analyzed through various techniques (NMR, MASS, FTIR, HPLC, and UV- spectrophotometer) for their bioactive secondary metabolites. Methods: In silico calculation was performed to reveal bioactive metabolites with the potential to be antibacterial, and their primary mode of action may include dissolving bacterial and fungal cell walls. Results: The antimicrobial activity of Adathoda beddomei was demonstrated against different pathogenic and non-pathogenic bacteria. Identification of endophytes was done based on external morphological characteristics with the help of a scanning electron microscope (SEM). Conclusion: Natural compounds derived from endophyte bacteria with a very low molecular mass can be used to discover new and important structures for different pharmaceuticals and agrochemicals.

Asafoetida, also known as Hing, is a resinous gum derived from the roots of Ferula species, specifically Ferula asafetida. From ancient times, it has been employed both in the kitchen as a seasoning and in the practice of traditional medicine. In terms of pharmacognosy, asafoetida is comprised of a number of active chemicals, the most notable of which are coumarins, volatile oils (17%), and ferulic acid (60%). Ferulic acid and coumarins (40%) are two of the components that contribute to the medicinal value of this plant. The volatile oils are responsible for the strong odour and flavour of this plant. It is used for a variety of applications in the medical field. It is not only used as spices and condiments for the goal of imparting taste in curries, but it is also utilised in the treatment of gastrointestinal tract diseases, asthma, whooping cough, hypertension, and a variety of other conditions. The herb has been used to extract a variety of phytochemical components, including sesquiterpene coumarins, coumarins, diterpene coumarins, and chemicals containing sulphur. This manuscript provides a synopsis of the facts concerning the pharmacological activities and bioactive components of Ferula asafetida.

Background: The leaves of Rhus chinensis Mill., a common deciduous tree found in the mild temperate zone of Asia, have many medicinal effects, including antioxidant properties. Objectives and Methods: This study aims to optimize the conditions for extracting phenols from Rhus chinensis Mill. (RCM) using a microwave-assisted extraction system with glycerol (MAEG) via response surface methodology (RSM). It also aims to compare the extraction efficacy of decoction and MAEG methods in terms of the bioactive compounds and antioxidant activities of the extracts obtained through them, identify bioactive compounds in both extracts via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-ESIQTOF- MS/MS), and determine the cytotoxicity and cellular antioxidant activity of MAEG extract. Results: Temperature and glycerol concentration significantly affected the total phenolic content (TPC) of the extracts. The validated value of TPC was 84.11 ± 4.28 mg GAE/g for the sample obtained under the optimal conditions of 12.76 min at 54.08°C and 34.48% glycerol concentration. MAEG extract exhibited higher antioxidant properties compared to the decoction extract. Different phenolic compounds in the extracts were tentatively identified by LC-QTOF. MAEG concentrations from 1 mg/mL to 7.5 mg/mL were considered non-cytotoxic to NIH/3T3 fibroblasts. Furthermore, the cell viability of NIH/3T3 fibroblasts increased after being treated with MAEG extract (from 2.5 mg/mL to 7.5 mg/mL) and subjected to H2O2- induced oxidative stress compared to H2O2 treatment alone. Conclusion: Finally, MAEG can be used as a novel green extraction method for obtaining bioactive compounds for cosmetic and medicinal applications.

Background: Thuja articulata is a Mediterranean forest species from the Cupressaceae family, it has been used in popular medicine to treat several diseases. Various studies have been carried out in vitro using diverse T. articulata extracts to understand its traditional use. Methods: In this study, the ethyl acetate extract of T. articulata trunk barks was chemically identified using HPLC-PDA-ESI-MS, then examined in vitro for its antioxidant and α-amylase inhibitory effects. A molecular docking study was also performed to reinforce the noted bioactivities. Results: HPLC-PDA-ESI-MS analysis led to the identification of 22 polyphenolic compounds in the ethyl acetate extract of T. articulata trunk barks. This extract revealed interesting in vitro antioxidant properties and a significant α-amylase inhibitory action (IC50 = 16.08 ± 1.27 μg/mL). In silico analysis was found to agree with the in vitro studies in which major constituents of the ethyl acetate extract revealed low binding energy and a correct mode of interaction in the active pocket of the enzyme (PDB: 7TAA). The anti-a-amylase potential could be due either to a synergistic or individual action of certain constituents present in this extract. Conclusion: This study illustrates that the ethyl acetate extract of T. articulata trunk barks has potent sources of antioxidants and α-amylase inhibitors to be explored.