Mini Reviews in Medicinal Chemistry - Volume 19, Issue 15, 2019

Cancer is the second leading factor of human death in the world. Long-term consumption of cooked red meat brings about various types of cancers like colorectal cancer due to the formation of Heterocyclic Aromatic Amines (HAAs) during the heating process of meat. There are various solutions for the reduction of these toxicants. The aim of this article is to describe probiotic as one of the possible strategies for bioremoval of these carcinogenic and mutagenic substances and change food to functional one as well. The mechanism of biodetoxification is binding by probiotics, which depends on some variables including the probiotic characteristics, kind and content of the mutagens, as well as some properties of media. In this article, after introducing detoxification ability of probiotics and listing of all reported probiotics in this field, the influencing variables are surveyed and finally, opportunities and problems of HAA bioremoval by probiotics are described.

As important marine biological resources, corals produce a large amount of active organic compounds in their secondary metabolic processes, including numerous brominated, chlorinated, and iodinated compounds. These compounds, with novel structures and unique activities, guide the discovery and research of important lead compounds and novel biological mechanisms. Through a large number of literature surveys, this paper summarized a total of 145 halogenated secondary metabolites which were roughly divided into four major classes of terpenes, prostaglandins, steroids and alkaloids, and they were mainly isolated from ten coral families, Ellisellidae, Gorgoniidae, Briareidae, Plexauridae, Anthothelidae, Alcyoniidae, Clavularidae, Tubiporidae, Nephtheidae and Dendrophyllidae to the best of our knowledge. In addition, their organism species, structure composition and biological activity were also discussed in the form of a chart in this essay.

Nowadays, heterocyclic compounds act as a scaffold and are the backbone of medicinal chemistry. Among all of the heterocyclic scaffolds, 1,4-Dihydropyridine (1,4-DHP) is one of the most important heterocyclic rings that possess prominent therapeutic effects in a very versatile manner and plays an important role in synthetic, medicinal, and bioorganic chemistry. The main aim of the study is to review and encompass relevant studies related to 1,4-DHP and excellent therapeutic benefits of its derivatives. An extensive review of Pubmed-Medline, Embase and Lancet’s published articles was done to find all relevant studies on the activity of 1,4-DHP and its derivatives. 1,4-DHP is a potent Voltage-Gated Calcium Channel (VGCC) antagonist derivative which acts as an anti-hypertensive, anti- anginal, anti-tumor, anti-inflammatory, anti-tubercular, anti-cancer, anti-hyperplasia, anti-mutagenic, anti-dyslipidemic, and anti-ulcer agent. From the inferences of the study, it can be concluded that the basic nucleus, 1,4-DHP which is a voltage-gated calcium ion channel blocker, acts as a base for its derivatives that possess different important therapeutic effects. There is a need of further research of this basic nucleus as it is a multifunctional moiety, on which addition of different groups can yield a better drug for its other activities such as anti-convulsant, anti-oxidant, anti-mutagenic, and anti-microbial. This review would be significant for further researches in the development of several kinds of drugs by representing successful matrix for the medicinal agents.

Objective & Methodology: New hybrids of thiopyrimidine-five/six heterocyclic rings were synthesized and in vitro evaluated for their antiproliferative activity against three human cancer cell lines, namely HCT116 (human colorectal carcinoma), PC-3 (human prostate adenocarcinoma) and HepG2 (human liver carcinoma) cell lines. The most potency was elicited by the target candidates against the viability of HCT116 cell lines. It was higher than that obtained by the positive control 5-Fluorouracil (IC50 range; 0.11-0.49 μM, IC50, 5-FU; 1.10 μM). Results: Cell cycle analysis and apoptosis activation revealed that compound 20 induced G2/M phase arrest and apoptosis in HCT116 cells. In addition, compound 20 activates the caspases-9 and -3, a process which might mediate the apoptosis of HCT116 cells. Quantitative structure activity relationship study was done and revealed a high predictive power R2 suggesting goodness of the models. Conclusion: Furthermore, there is a good agreement between the observed pIC50 and the predicted pIC50 values, in addition, the low RMSD and standard error values indicate the accuracy of the model. Antimicrobial evaluation revealed that some of these compounds exhibited significant activities against the tested pathogenic bacteria and fungi, wherein compounds 7a, 14, 15a, 21a, produced the most potent and broad spectrum antibacterial and antifungal potency that was equivalent to that revealed by Vibramycin and Ketoconazole (MIC; 125 μg/mL). Moreover, compounds 15a, 21c, investigated dual potent antimicrobial and anticancer activity.

Background: bis-heterocycles especially those containing pyrazole moiety display much better antibacterial activity than mono heterocycles. Objective: Herein, we synthesised a series of new bis-pyrazoles and investigated their antimicrobial agents. Methods: A novel series of bis-pyrazole derivatives have been synthesized in good yield by coupling reaction of cyanoacetic acid {4-[(2-cyano-acetyl)-hydrazonomethyl]-benzylidene}-hydrazide with a number of diazonium salts of aromatic amines in DMF in the presence of NaOH. Refluxing of the produced hydrazones with hydrazine-hydrate in ethanolic solution afforded the respective bis-pyrazoles. On the other hand, the reaction of bis(cyanoacetic acid hydrazide) derivative with a diversity of hydrazonoyl chlorides in dioxane under reflux gave bis-pyrazoles. Results: The structures of all the products were discussed and assured from all possible spectral data as well as for the elemental analysis. In addition, the results of the antimicrobial activity examination of selected derivatives revealed a high strength of some tested compounds compared to standard bactericides and fungicides utilized. Molecular docking of the newly synthesized compounds into the Enoyl ACP reductase active site supported the in vitro antimicrobial activity. All the tested compounds could fit in the enzyme binding pocket with significant binding affinities (-7.040 to -9.141 Kcal/mol). Conclusion: The good results of the antimicrobial examination of the newly synthesized bis-pyrazoles comprise the considerable evidence of the importance of bis-heterocyclic compounds which encourages us to continue designing and synthesising a novel series with potent biological activity in the future.