Medicinal Chemistry

Pyrazole derivatives have their own importance in aromatic organic heterocycle family. Application of these derivatives in chemistry and biology has attracted increasing interest occupy a unique place in field of medicinal chemistry due to their wide spectrum of biological activities. There are known for their anticancer, antiviral, antibacterial, antifungal, analgesic and anti-inflammatory and activities and so on. Due to the importance of this chemical skeletons, the present review reports the recent progress (2010-2016) on the biological activities of some monodentate, bidentate, tridentate and tetradente compounds based on pyrazole moieties and containing NCN bonds which connecting between the pyrazole and amine unit.

A series of substituted quinazolin-4(3H)-ones (VIII1-12) have been synthesized by treating 3-amino-2- benzylamino-substituted- quinazolin-4(3H)-one VII1-4, with different aldehydes. The starting material 3-amino-2- benzylamino substituted- quinazolin-4(3H)-one VII1-4 was synthesized by nucleophilic substitution of thiomethyl group of 3-amino-2-methylthio-substituted- quinazolin-4(3H)-one VI1-4 with benzylamine. The synthesized compounds VIII1-12 was investigated for analgesic activity. All the test compounds exhibited significant analgesic activity in comparison with paracetamol.

Background: The starfishes were shown to containe the bioactive compounds which exhibit various biological activities including cytotoxicity, antiinflammatory, hemolytic, antibacterial, antiviral, and antifungal effects.

Objective: To determine the anti-inflammatory activity and cytotoxicity of the extracts of four different starfishes.

Materials and methods: The homogenized fresh body component of starfishes were extracted and concentrated. The EtOH extract of A. pectinifera with high extraction yield and total phenol was partitioned using different extraction solvents. The CHCl3 fraction was further fractionated using thin-layer chromatography, silica-gel chromatography, gel filtration, and recycling preparative HPLC, in that order.

Results: Fraction SAP4.2.5 exhibited strong anti-inflammatory activity without cytotoxic effect up to a concentration of 25 μg/mL, and high cytotoxicity, with IC50 values of 19.4, 34.8, and 32.7 μg/mL against AGS, DLD-1, and HeLa cells, respectively. These biological activities could be due to the presence of lathosterol, 13-tetradecen-1-ol acetate, and stigmast-7-en-3-ol (3ß,5α,24S)-like compounds.

Conclusion: Starfish has a great potential as a resource for natural health products because of its strong antiinflammatory and anticancer activities.

Salicylic acid (SA) derivatives are widely used for treatment of various diseases. Acetylsalicylic acid represents the most widely used drug in the world, 4-Aminosalicylic acid (4-ASA) was historically used as a systemic antituberculosis drug as well as diflunisal is a strong pain killer and antipyretic. 5-Aminosalicylic acid (5-ASA) which had been synthesized at the end of 19th century and employed first for the production of azo dyes, was then identified as a very valuable medicinal agent as well as part of many biologically active agents. 5-ASA is not metabolized to salicylic acid for pharmacological activity. It is not considered a true salicylate. In contrary to other salicylates, 5-ASA doesn’t induce upper gastrointestinal (GI) side effects. Moreover, It was found, especially, useful for treatment of inflammatory bowel diseases (IBD). It is unique among salicylates and has a broad specrum of biological activities including, anti-inflammatory, analgesic, neuroprotective and antitumor. Since we are interested in this compound and its derivatives, we prepared this review to give insight into its chemistry, anti-inflammatory activity, in particular, for treatment of IBD. Different approaches for colonic targeting of 5-ASA w ill be covered with emphasis on chemical methods as well as its proposed mechanisms of action.

In this review we refer to a promising family of molecules in the fight against Chagas disease. Terpene derivatives are abundant in the plant Kingdom and in the last years many compounds have shown important biological activities. Diterpenes and sesquiterpene lactones have shown in vitro and in vivo trypanocidal activity and they emerge as potential antichagasic drugs. These molecules may act on these parasites by multiple mechanisms, as it has been reported. Moreover, given the chemical structure of these compounds it is feasible to modify these molecules by chemical substitution in order to optimize their action against parasites.

Rupestonic acid is the main active compound in Artemisia rupestris L, which mainly grows in Xinjiang of China. To find its active group, a series of novel rupestonic acid 3-carbonyl analogues were prepared. The structures of the compounds were confirmed by spectral and high resolution mass spectrum. All compounds were evaluated for antiviral activity against influenza A (H3N2 and H1N1) and B viruses in MDCK cell cultures. The compounds displayed a confined structure-activity relationship. Compound 13 with allyl group was the most potent inhibitor against influenza A/H1N1 virus with an IC50 value of 4.27 μM and a SI value of 27.04. Dihydrogen amide 3 possesses the good potency against influenza B virus with an IC50 value of 5.5 μM and a SI value of 13.

P-coumaric acid (p-CA), which was widely found in nutritious plant foods, has various anti-inflammatory effects in vivo. In order to clarify the anti-inflammatory mechanisms, the effects on lipopolysaccharide (LPS)-stimulated inflammatory responses in RAW264.7 macrophage cells were examined by pretreated with P-CA (10-100 μg/ml). P-CA signiï¬Ã‚cantly inhibited iNOS, COX-2, IL-1β and TNF-α expression at mRNA and/or protein level. Furthermore, P-CA suppressed the phosphorylation of IκB and ERK1/2. The above results suggest that P-CA may inhibit the production of inflammatory cytokines induced by LPS through blocking NF-kB and MAPKs signaling pathways, which further support the anti-inflammatory and immunomodulatory potential of P-CA in different models of inflammation.

Current research has supported the potential of plant-derived natural compounds for the treatment and prevention of cancer and ursolic acid (UA) is one such compound. Unraveling the molecular mechanism of the protective effects of UA could establish a novel foundation to treat cancer. Studies have demonstrated that UA targets intracellular and extracellular molecules that are responsible for processes such as apoptosis, metastasis, autophagy, angiogenesis, oxidative stress, and inflammation. UA can reportedly be used as a potential drug when integrated with modern technological advancements to treat cancer and other diseases. In this review, the availability, chemical structures and properties, bioactivity, and the different molecular mechanisms of UA against cancer are compiled to understand the multiple aspects as well as the limitations of this potential treatment.

Herein we report development and validation of the method for evaluating the encapsulation efficiency of a micelle-based nanosystem composed of irinotecan hydrochloride (CPT-11) and an amphiphilic molecule DSPEmPEG2000. The results showed that the centrifugation method can be used for separation of free drug, a critical step in measuring encapsulation efficiency, and the EE of three batches of CPT-11/DSPE-mPEG2000 micelles was 90.0% ± 1.0%. The results also indicated that the conditions used in the process have to be optimized to acquire reliable data.

For amyloid fibril cross-β structures of Aβ human protein, we find theoretical calculations are agreeing with laboratory X-ray crystallography experiments. This mini article summarized mathematical formulas of amyloid fibril cross-β structures of segments of human Aβ protein. These formulas are accurate and correct some data in the Protein Data Bank (PDB). However, more mathematical formulas for core Chains AB (PDB IDs: 3OW9, 3PZZ, 2OKZ), or ABGH (PDB IDs: 3OVJ, 2Y3J, 2Y3K, 2Y3L) (or ABCD (PDB ID: 2ONA)) are still needed to present and optimize.

A new class of heterocycles, (3-7) specifically substituted pyrazolo-, isoxazolo- and pyrimidocycloocta[b]indoles, has been synthesized by condensation of substituted 7-(hydroxymethylene)-5,7,8,9,10,11-hexahydrocycloocta[b] indol-6-ones (2) with hydrazine hydrate, hydroxylamine hydrochloride, phenylhydrazine, urea and thiourea, respectively. The structures of the compounds were established by IR, 1H NMR, 13C NMR and the compounds have been screened for in vitro antibacterial and antitumor activities against two human cancer cell lines (A549 and MCF7). Among the compounds screened, 6b and 7b emerged as the most active anti bacterial and the most potent anti proliferative compounds against both the tested cell lines. Structure activity relationship (SAR) analyses confirmed that these two compounds are potential lead for future drug discovery studies.

Capsaicin, the major component of chili peppers, has shown potential therapeutic effect against metabolic disease inducing weight loss. Its effect is exerted by a particular molecular mechanism and pharmacodynamics, distinct to current obesity treatments. However, its high irritating taste or pungency has limited its use to some clinical trials. Capsaicin-like molecules, known as capsaicin synthetic analogs, contain the majority of capsaicin domains but without those of pungency. Recently, they have received much attention by their potent antiobesity effect. The study of their structure-activity relationship would unravel the mechanisms responsible of this effect. This review summarizes much of the current experimental evidence of the potential effect in metabolism regulation of natural and synthetic capsaicin analogs discovered to date.