Medicinal Chemistry Research最新文献

Herein, the privilege in favor of biological importance of indole-containing scaffolds related to the semi-synthetic and extracted from natural sources is summarized. Such compounds have shown notable medicinal significance and are used in the treatment of various carcinomas after FDA approval. The chemistry of indoles’ skeleton derivatives showed various conformations at specific conditions, including tautomerization, when they came into contact with polar solvents; consequently, such phenomena are responsible for enhancing the biological effect on enzymes. In the foregoing review study in the past decade, we demonstrated the biological significance and the transformation of drug analysis owing to resonating structures. Functionalize groups, it was noted that pi-bonds-unsaturated functions, sp^1/2/3 hybridized methylene groups, cyclic ethers, primary amino groups, halogens, and staggered conformations displayed the most potent active drug-like molecules. The aim of this report is that drugs like lead molecules could be derivatized for the discovery of more effective drugs on the basis of their possible active sites on the surface in the future.

The genus Plumeria of the Apocynaceae family has a rich history of traditional medicines supported by empirical evidences. This review consolidates diverse biological attributes, phytochemical compositions, physical properties (melting point, shape, optical rotation, etc.), and analytical data (UV, IR, Mass spectroscopic data, elemental analysis) of various species of Plumeria. The review covered the chemistry of wide range of natural compounds like iridoids, triterpenoids, alkaloids, flavonoids, steroids, cardiac glycosides, quinones, anthocyanins, cardenolides, fatty acid esters, lignans, coumarins, etc. found in various species of the genus Plumeria. Analytical techniques including chromatography, IR, UV, and mass spectroscopy have significantly contributed to elucidating the complex chemical profiles of extracts of various species of Plumeria which are systematically presented in a tabular format. The review also defines the historical background, geographical distribution, and traditional uses of various species of the genus Plumeria. The review also includes the mechanisms of action and biotransformation of compounds, providing a deeper understanding of their therapeutic potential. The comprehensive review reveals the significance of the natural products isolated from a number of species of genus Plumeria. It is also suggestive that there is an extensive scope for further investigation to explore new therapeutic components of the genus Plumeria.

Tuberculosis (TB) is a contagious disease caused by M. tuberculosis (Mtb) affecting people across the globe. Quinoline and chalcone cores have good anti-tubercular properties; thus, we have designed a hybrid scaffold containing quinoline and chalcone. A series of 3-(quinolin-3-yl)-1-phenylprop-2-en-1-one analogs 7a-p and 8a-k were synthesized through different reactions involving nucleophilic substitution, Vilsmeier Haack formylation, Claisen Schmidt condensation, and demethylation. Spectroscopic methods, including ¹H NMR, ¹³C NMR, IR, and HRMS, were used to characterize all synthesized compounds. The anti-tubercular activity of compounds 7a-p and 8a-k was assessed against Mtb H₃₇Rv (ATCC 27294). These compounds demonstrated anti-tubercular activity against H₃₇Rv in the range of 6.25–50 μM. Swiss ADME’s in silico computational studies showed that the ADME parameters were better and had a good pharmacokinetic profile. The compounds 8a, 7a, and 7p showed the most potential as anti-TB activity against Mtb H37Rv in this study, with MIC values of 6.25 μM, 12.5 μM, and 10 μM, respectively.

Salidroside (Sal), a natural phenolic glycoside ubiquitous across all species of the Rhodiola genus, has garnered considerable attention in contemporary pharmacological research. Its multifaceted pharmacological profile encompasses anti-tumor, anti-hypoxia, anti-inflammatory, and anti-atherosclerotic properties, among others. Notably, its pharmacological repertoire extends to safeguarding against hypoxic injury, particularly in high-altitude environments. Furthermore, Sal serves as a key indicator for assessing the quality of Rhodiola. It is capable of exerting biological activity on the nervous system, cardiovascular system and internal organs of the body through various pathways and mechanisms, and thus has the potential to be therapeutically effective in the treatment of diseases associated with these systems. In order to optimize the effectiveness and safety of Sal’s application and ensure the isolation of highly pure and stable monomer components, its extraction and purification processes were refined. In addition, it is important to protect wild plant resources and meet market demand, as well as to explore Sal and its synthetic products, in consideration of its anti-altitude anoxia biological characteristics. Therefore, this paper reviewed the source, extraction and purification, pharmacological effects, biological activity, synthesis and product application of Sal, updated and deepened the understanding of Sal, and provided theoretical basis for the further research of Sal.

A set of sesamol-derived acetamides was designed, synthesized, and evaluated against monoamine oxidases (MAO-A and MAO-B) and cholinesterases (AChE and BChE) for targeting neurodegenerative diseases. Most of the tested compounds showed inhibition activity at micromolar to nanomolar ranges. The 3,4-dichoro derivative (compound 19) was the most potent MAO-A inhibitor (IC₅₀ = 0.053 ± 0.001 µM) while the 4-methyl analog (compound 16) emerged as a lead MAO-B inhibitor (IC₅₀ = 0.019 ± 0.001 µM) compared to the reference inhibitors clorgyline (MAO-A IC₅₀ = 0.096 ± 0.003 µM) and selegyline (MAO B IC₅₀ = 0.021 ± 0.002 µM). Further, the 2,4-dichloro analog (compound 20) emerged as a potent dual MAO (MAO-A IC₅₀ = 0.160 ± 0.009 µM, MAO-B IC₅₀ = 0.071 ± 0.002 µM) and ChE (AChE IC₅₀ = 2.611 ± 0.086 µM and BChE IC₅₀ = 4.22 ± 0.162 µM) inhibitor. Moreover, molecular simulation studies revealed that H-bonding and hydrophobic interactions stabilize the virtual lead inhibitor-protein complex. Selected MAO-ChE inhibitors showed significant antioxidant and iron-chelation properties, suggesting their potential in treating neurological disorders characterized by impaired iron homeostasis. In summary, the structural modification attempted in the present study yielded a few nanomolar MAO (MAO-B) inhibitors and, thus, provided new insights into the linker requirements for dual MAO/ChE inhibitory properties.

Colorectal cancer is one of the most incident and lethal cancers in the world. The search for new compounds to treat this disease is being motivated by the occurrence of side effects and the rising in the resistance to chemotherapy. We synthesized a new class of conjugates bearing quinazolinone and melatonin which were prepared in good yields (63–93%) through one-pot three-component approach. quinazolinone/melatonin conjugates were proved against SW480 human colorectal adenocarcinoma cells and non-malignant colonic cells (NCM460). The cytotoxic and antiproliferative activities were determined through the sulforhodamine B assay. Compounds 1f, 1g and 1i–l displayed the best activity, being hybrids 1i–l the most selective against malignant cells, causing either a cytostatic and/or cytotoxic effect with evident morphological changes. Moreover, a theoretical drug-like/pharmacokinetics/toxicological study suggested that the hit-promising compounds 1i and 1j would have a great chance to advance to further preclinical studies as anti-cancer therapeutic candidate for oral oncological management. Our study evidently identified the potency of these quinazolinone/melatonin hybrids to be a prototype drug for further investigations toward novel therapeutics treatments of colorectal cancer.