Current Bioactive Compounds - Volume 18, Issue 9, 2022

Background: Inflammatory response is the body’s first-line defence mechanism in which the immune system recognises, counters the antigens, and aids in healing the disease. The World Health Organisation suggests that inflammation is one of the greatest causes of death in the world. Inflammation could be acute or chronic due to the release of inflammatory mediators, i.e. prostaglandins, leukotrienes due to mitogens, and antigens or cytokines found in the body. Methods: The detailed studies and conceptual framework of dual COX/LOX inhibitors of natural origin have attracted great attention. A bibliographic database using PubMed cites for peer-reviewed research articles with titles containing dual COX-2 and 5-LOX enzyme inhibitors, heterocyclic moieties, with AND Boolean operator's terms for the last ten years was searched. The quality papers reviewing the natural or synthetic lead compounds were extracted. Results: Out of 127 research and review articles evaluated, 54 articles were cited for providing high-quality data regarding the pharmacoactive molecules having anti-inflammatory activity via dual COX-2/5-LOX inhibition. In addition, in silico and experimental studies on dual COX/LOX inhibitors in increasing hierarchical order over the past decade were illustrated. Conclusion: This review provides details of isolated bioactive compounds, such as pyrazole, coumaperine, indoles, and phenanthrene derivatives, that have been significantly reported for anti- inflammatory activities.

Background: Sanguinarine, a benzophenanthridine alkaloid extracted from Sanguinaria canadensis has been found to show an inhibitory role on proapoptotic and growth inhibitory activities in various tumor cells of experimental subjects. Objective: This review highlights and summarizes the effects of sanguinarine against cancers alongside the possible mechanisms involved as depicted in various in vitro and in vivo models. Results: Sanguinarine shows anticancer activities via various mechanisms like inhibiting cancer cell proliferation, aberrantly activated signal transduction pathways, sang-mediated angiogenesis, and induction of cell death and tumor suppressors’ expressions. It also enhances the cytotoxic effects of chemotherapeutics via sensitizing cancer cells against these drugs, hence improving their pharmacological attributes. Conclusion: Due to the significant role of sanguinarine against various types of cancer, it can be explored for its potential functions in cancer treatment.

Natural products have stimulated the interest of chemists owing to their abundant structural diversity and complexity. Indeed, natural products have performed an essential role, particularly in the cure of cancerous and infectious diseases, thereby providing medicinal researchers with several unexplored chemotypes for the innovation of new drugs. Fusion of chemical derivatization and combinatorial synthesis forms the basis of the concept of chemo diversification of plants. Diverse libraries of natural product analogs are constructed through existing biological and chemical approaches using unique schemes to expand natural product frameworks. This review aims to present several approaches employed to offer innovative opportunities to synthesize NP-inspired compound libraries. Reactive molecular fragments present in most natural products are chemically converted to chemically engineered extracts (CEEs) or semisynthetic compounds constituting distinct libraries. Bio-guided isolation for natural products required vital tools like reverse phase chromatography and bioautographic assays. Different established strategies from DTS, BIOS, CtD, FOS, FBDD to late-stage diversification facilitate the expansion of molecules with physicochemical properties. In particular, fragment-like natural products with novel skeletons may be used as preliminary points for chemical biology and medicinal chemistry programs with great capacity. In this review, we sum up how NPs have proven fruitful for the novel methodologies responsible for the diversification of complex natural products; therefore, it is worth going over the upcoming integration of natural products with combinatorial chemistry.

Objectives: the synthesis of 4-((1-phenyl-3-(substitutedphenyl)-1h-pyrazol-4-yl) methylene)- 4h-pyrazol-3,5-diamine and 3-amino-4-((1-phenyl-3-(substitutedphenyl)-1h-pyrazol-4-yl) methylene)-1h-pyrazol-5(4h)-one was designed and performed very aptly in deep eutectic solvent system. Methods: the utilization of deep eutectic solvent (des) system chcl/gly (1:2) in the absence of hazardous organic co-solvents, an efficient multicomponent one-pot synthetic strategy has been advanced. In addition to that, from the perspectives of sustainable developments in organic synthesis, the deep eutectic solvent system was recovered and very efficiently reused up to four cycles. Results: it has been observed that the efficacy of the deep eutectic solvent was decreased after the second cycle, which has a measurable impact on the yield of the reaction. Conclusion: furthermore, the synthesized aminopyrazole and aminopyrazolone compounds were screened as antibacterial and antifungal agents.

Background: Buriti (Mauritia flexuosa) oil has high economic potential because it contains monounsaturated and polyunsaturated fatty acids with high antioxidant potential and high carotenoid content, making it an excellent source of pro-vitamin A. Objective: The objective of this work was to evaluate the rheological properties of filmogenic solutions incorporated with different buriti oil concentrations. Methods: Buriti oil (0.15 to 0.45% w/v) and emulsifier (Tween®20) (0.02 to 0.04% w/v) were combined using a factorial experimental design 2² with 3 central points for the preparation of filmogenic solutions with cassava starch (3%, w/v) and glycerol (0.06%, w/v). Rheological properties, static and centrifugation emulsion stabilities, and pH value of filmogenic solutions were evaluated. Results: Filmogenic solutions with lower emulsifier concentration showed increased flow resistance and non-Newtonian and pseudoplastic behavior (n<1). Central point formulation (E, F, and G) remained stable (no particle agglomeration) throughout the test period, as well as pH value close to neutrality. In centrifugation stability index at 3500 rpm, only formulation C did not show phase separation. Conclusion: It was possible to develop a mixture of a filmogenic solution containing buriti oil that could be applied as an eco-friendly coating in food.

Background: Chalcones are open-chain flavonoids especially attractive to medicinal chemistry due to their easy synthesis and the possibility of structural modifications. Objective: This study aims to evaluate the in vitro anticancer activity of a series of hybrids chalcones- thiosemicarbazones against the human hepatocellular carcinoma cell line HepG2. Methods: Seven hybrid chalcones-thiosemicarbazones (CTs), 3-(4’-X-phenyl)-1-phenylprop- 2-en-1-one thiosemicarbazone, where X=H (CT-H), CH3 (CT-CH3), NO2 (CT-NO2), Cl (CTCl), CN (CT-CN), F (CT-F), and Br (CT-Br), were synthesized and their effects on cells’ viability and mitochondrial oxygen consumption were assessed. Results: Incubation with CTs caused a decrease in HepG2 cells viability in a time-concentration-dependent manner. The most effective compounds in inhibiting cell viability, after 24 hours of treatment, were CT-Cl and CT-CH3 (IC50 20.9 and 23.63 μM, respectively). In addition, using 10 μM and only 1 hour of pre-incubation, CT-CH3 caused a reduction in basal respiration (-37 %), oxygen consumption coupled with ATP synthesis (-60 %), and maximum oxygen consumption (-54 %). These alterations in respiratory parameters may be involved with the inhibitory effects of CT-CH3 since significant changes in oxygen consumption rates were observed in a condition that anticipates more significant losses of cell viability. The ADME parameters and the no violation of Lipinski Rule of Five showed that all compounds are safe. Conclusion: These results may contribute to the knowledge about the effects of CTs on these cells and the development of new treatments against HCCs.

Thiazole and the related nuclei constitute one of the most significant moieties in the extensively emerging domain of heterocyclic compounds. The versatile nature of the thiazole nucleus can be determined as it is present in natural products like vitamin B1. Furthermore, its derivatives exhibit diverse biological activities, including antimicrobial, anticancer, antihistaminic, antioxidant, etc. They have also emerged as potent CNS agents and are primarily used in the treatment of various CNS disorders. The structure-activity relationship of various amine derivatives of ethylated thiazole demonstrates their use as potential agents in the treatment of melanoma, pigmentation as well as solar elastosis. Thiazole fused with different heterocyclic systems results in many novel derivatives with higher therapeutic activity. Benzothiazole and Thiazolopyrimidine have a distinct position in this regard. This review focuses on the central role of thiazole and its derivatives in current drug design, covering a broad spectrum of pharmacological activities associated with them.