International Journal of Medicinal Chemistry最新文献

Phytochemicals from Dicerocaryum senecioides were studied for hair rejuvenation activity using BalB/c mice. Solvent extractions and thin layer chromatography (TLC) were used to extract and isolate the phytochemicals respectively. Phytochemicals were identified by spraying with target-specific revealing reagents. In vivo hair growth stimulating activity for each extract was tested on denuded dorsal skin of 5-week old BalB/c mice against the controls and the standard drug minoxidil. The parameters used to evaluate hair growth were hair growth completion time, hair length, hair weight, hair follicle length, and relative hair follicle area. The identified phytochemicals from the active ethanol extract were steroidal glycosides, triterpenoid glycosides, and flavonoid glycosides. Flavonoid glycosides treatment had the uppermost hair rejuvenation capacity as measured by the shortest hair growth completion time (19 days) versus control (29 days) and longest hair length (11.04 mm and 11.86 mm for male and female mice respectively while the control group had 5.15 mm for male mice and 5.33 mm for female mice). Hair growth stimulation by flavonoid glycosides was also dependent on dose concentration. It can be concluded from this study that flavonoid glycosides extracted from the leaves of Dicerocaryum senecioides have remarkable hair rejuvenation capacity in BalB/c mice. The present results provides insights on the use of Dicerocaryum senecioides for hair rejuvenation in traditional practices and on the potential of the plant as a source of novel compounds that can be used as hair growth promoters.

The purpose of this study was to evaluate the physicochemical properties of piperine (PP) in ground mixtures (GMs) of PP with α-, β-, or γ-cyclodextrin (CD) under conditions of humidity, heat, and humidity-heat. In solid-state fluorescence measurements, the fluorescence maxima for GM (PP/αCD = 1/2), GM (PP/βCD = 1/1), and GM (PP/γCD = 1/1) were observed at 463, 472, and 469 nm, respectively. On the other hand, the humidified GMs exhibited maxima at 454, 460, and 465 nm, while the humidified-heated samples displayed fluorescence maxima at 455, 455, and 469 nm, respectively. Therefore, the molecular behavior of PP with α, β, and γCD was concluded to vary upon the coordination of water molecules. NIR and solid-state fluorescence measurements revealed that the molecular behavior of PP inside the α, β, and γCD cavity changed by water and heat factors depends on the mobility of the methylenedioxyphenyl group.

Allylic acetates derived from Baylis-Hillman reaction undergo efficient nucleophilic isomerization with imidazoles and triazoles to provide imidazolylmethyl and triazolylmethyl cinnamates stereoselectively. Antifungal evaluation of these derivatives against Cryptococcus neoformans exhibits good minimum inhibitory concentration values. These compounds exhibit low toxicity in proliferating MCF-7 breast cancer cell line. Structure activity relationship studies indicate that halogenated aromatic derivatives provide better antifungal activity.

X-ray and neutron crystallography are powerful techniques utilized to study the structures of biomolecules. Visualization of enzymes in complex with substrate/product and the capture of intermediate states can be related to activity to facilitate understanding of the catalytic mechanism. Subsequent analysis of small molecule binding within the enzyme active site provides insight into mechanisms of inhibition, supporting the design of novel inhibitors using a structure-guided approach. The first X-ray crystal structures were determined for small, ubiquitous enzymes such as carbonic anhydrase (CA). CAs are a family of zinc metalloenzymes that catalyze the hydration of CO₂, producing HCO₃ ^- and a proton. The CA structure and ping-pong mechanism have been extensively studied and are well understood. Though the function of CA plays an important role in a variety of physiological functions, CA has also been associated with diseases such as glaucoma, edema, epilepsy, obesity, and cancer and is therefore recognized as a drug target. In this review, a brief history of crystallography and its impact on CA research is discussed.

Some species of the Baccharis genus have been shown to possess important biomedical properties, including cytotoxic activity. In this study, we examined the cytotoxic effect of methanol extract from Baccharis obtusifolia (Asteraceae) in cancer cell lines of prostate (PC-3), colon (RKO), astrocytoma (D-384), and breast (MCF-7). The methanolic extract displayed the largest substantial cytotoxic effect in lines of colon cancer (RKO) and cerebral astrocytoma (D-384). Chromatographic purification of the B. obtusifolia methanolic extract led to the isolation and identification of 5,4'-dihydroxy-7-methoxyflavone (1) and 5-hydroxy-7,4'-dimethoxyflavone (2) compounds of the flavonoid type.

Acquired Immunodeficiency Syndrome (AIDS) has been devastating for millions of people around the world. Inhibition of the human immunodeficiency virus (HIV) protease is among the most important approaches for the therapeutic intervention in HIV infection. Since the discovery of the HIV-1 protease, this enzyme has been considered as a key target for the inhibition of viral replication. A large body of research has been done to develop an effective HIV-1 protease inhibitor. There are to date 10 HIV-1 protease inhibitor drugs approved by the Food and Drug Administration (FDA) that have improved the survival and quality of life of HIV infected people. These drugs are prescribed in combination with the reverse transcriptase inhibitors, which is referred to as highly active antiretroviral therapy (HAART). The HIV-1 protease inhibitors play a vital role in HAART. The applications of click chemistry are dispersing in the field of drug discovery. Recently, click chemistry has captured a lot of attention and has become a powerful tool for the synthesis of medicinal skeletons in the discovery of anti-HIV drugs. Click reaction is a well-known method for making carbon-heteroatom-carbon bonds. Click reactions are popular because they are wide in scope, of high yielding, quick to perform, and easy to purify. In this review, we outlined current approaches towards the development of HIV-1 protease inhibitors employing click chemistry.

Carbonic anhydrases (CAs) are thought to be important for regulating pH in the tumor microenvironment. A few of the CA isoforms are upregulated in cancer cells, with only limited expression in normal cells. For these reasons, there is interest in developing inhibitors that target these tumor-associated CA isoforms, with increased efficacy but limited nonspecific cytotoxicity. Here we present some of the biophysical, biochemical, and cell based techniques and approaches that can be used to evaluate the potency of CA targeted inhibitors and decipher the role of CAs in tumorigenesis, cancer progression, and metastatic processes. These techniques include esterase activity assays, stop flow kinetics, and mass inlet mass spectroscopy (MIMS), all of which measure enzymatic activity of purified protein, in the presence or absence of inhibitors. Also discussed is the application of X-ray crystallography and Cryo-EM as well as other structure-based techniques and thermal shift assays to the studies of CA structure and function. Further, large-scale genomic and proteomic analytical methods, as well as cell based techniques like those that measure cell growth, apoptosis, clonogenicity, and cell migration and invasion, are discussed. We conclude by reviewing approaches that test the metastatic potential of CAs and how the aforementioned techniques have contributed to the field of CA cancer research.

The design, synthesis, and development of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are respectable area of research. Novel Diclofenac Schiff's bases (M1, M2, M4, M7, and M8) were designed and synthesized, and their respective chemical structures were deduced using various spectral tools (IR, ¹H NMR, ¹³C NMR, and MS). The compounds were synthesized via Schiff's condensation reaction and their anti-inflammatory activity was investigated applying the Carrageenan-induced paw edema model against Diclofenac as positive control. Percentage inhibition of edema indicated that all compounds were exhibiting a comparable anti-inflammatory activity as Diclofenac. Moreover, the anti-inflammatory activity was supported via virtual screening using molecular docking study. Interestingly compound M2 showed the highest in vivo activity (61.32% inhibition) when compared to standard Diclofenac (51.36% inhibition) as well as the best binding energy score (-10.765) and the virtual screening docking score (-12.142).

A new trisazo dye has been synthesized by coupling the diazonium ion of 3-amino-4H thieno[3,4-c][1]benzopyran-4-one with 2-tert-butyl-4-methoxyphenol. The newly prepared trisazo dye was characterized by its physical, elemental, and spectroscopic data. 2D-NMR (COSY, HSQC, and HMBC) techniques were used to secure the structural assignments. The new trisazo dye (compound 7) along with precursors 3, 4, and 6 was screened by microdilution susceptibility assay for antibacterial and antifungal activities towards eight bacterial strains and three yeasts selected on the basis of their relevance as human pathogens. The results showed that compound 7 (MIC = 2-128 μg/mL) was the most active as compared with its precursors. The most resistant microorganisms were V. cholerae NB2 and V. cholerae SG24, whereas the most sensitive microorganism was C. neoformans. The overall results of this study indicated that compound 7 had the greatest potential value against both yeasts and multidrug-resistant bacteria, so further investigation is warranted.