Leishmaniasis, Chagas disease and African sleeping sickness have been considered some of the most important tropical protozoan afflictions. As the number of drugs currently available to treat these human illnesses is severely limited and the majority has poor safety profiles and complicated administration schedules, actually there is an urgent need to develop new effective, safe and cost-effective drugs. Because quinoline alkaloids with antiprotozoal activity (quinine, chimanine, cryptolepine or huperzine groups) were historically and are still essential models for drug research to combat these parasitic infections, synthetic or semi-synthetic quinoline-based molecules are important for anti-kinetoplastid drug design approaches and synthetic methods of their preparation become a key task that is the central subject of this review. Its goal is to highlight the advances in the conventional and current syntheses of new 2-(3,4)-alkenyl (aryl) quinoline derivatives, which kill the most important kinetoplastid protozoa, – Leishmania and Trypanosoma and could be useful models for antileishmanial and antitrypanosomal research. An attempt has been made to present and discuss the more recent contributions in this field over the period 2015–2019, paying special attention to molecular design, synthetic efforts to new green reaction conditions for classical methods such as Skraup synthesis, Friedländer synthesis, Conrad–Limpach, Doebner–Miller, as well as contemporary methods like Gould–Jacobs, Meth–Cohn and Povarov reactions. This review includes brief general information on these neglected tropical diseases, their current chemotherapies, and primary natural models (quinoline alkaloids), suitable for development of anti-kinetoplastid quinoline-based agents. The main part of the review comprises critical discussion on the synthesis and chemistry of new quinolines diversely substituted by alkyl (alkenyl, aryl) fragments on the pyridine part of the quinoline skeleton, which could be considered interesting analogues of chimanine alkaloids. The methods described in this review were developed with the aim of overcoming the drawbacks of the traditional protocols using revolutionary precursors and strategies.

Fused pyrrolo[2,1- a ]isoquinolines have emerged as compelling molecules with remarkably potent cytotoxic activity and topoisomerase inhibitors.

Recent developments in the use of natural product-based molecules as antiparasitic agents for Malaria, leishmaniasis (LE), Chagas disease (CD), and Human African trypanosomiasis (HAT) are reviewed. The role of diverse plants in developing bioactive species is discussed in addition to analyzing the structural diversity of natural products as active agents and the diverse biological applications in CD, HAT, LE, and Malaria. This review focuses on medicinal chemistry, emphasizing the structural characteristics of natural molecules as bioactive agents against parasitic infections caused by Leishmania, Trypanosoma, and Plasmodium parasites.

In this study, a series of nineteen 2-arylquinolines and 4-acetamido-2-methyl-1,2,3,4-tetrahydroquinolines 4–22 was prepared using Povarov reaction protocols and their in vitro cytotoxicity was tested against human cancer cell lines, HeLa, PC3, MCF-7, and SKBR-3, compared with human dermis fibroblasts as non-tumor cells. In general, these quinoline derivatives displayed compelling selective anticancer properties. It was found that the 2-arylquinoline derivatives 4–16 displayed a better activity profile against the cell lines evaluated than the 2-acetamido-2-methyl-THQs 17–22. Particularly, C-6 substituted 2-phenylquinolines 4–10 and 2-(3,4-methylenedioxyphenyl)quinolines 11–16 displayed important activities against the evaluated cell lines, highlighting the results obtained generally against PC3 and HeLa. At the same time, MCF-7 and SKBR-3 cells were much less sensitive to them. Quinoline 13 and tetrahydroquinoline 18 showed selective cytotoxicity with IC₅₀ values of 8.3 μM and 13.15 μM, respectively, in cervical epithelial carcinoma, while quinolines 12 and 11 displayed good cytotoxicity with considerable IC₅₀ values (31.37 and 34.34 μM) in prostate sarcoma. All these compounds (except 11) stand out due to their low unspecific cytotoxicity presenting a remarkable selectivity (SI = 36.21–113.08) compared to doxorubicin. According to the ADME profiling, aromatic quinolines 4–16 are more lipophilic molecules (c Log P = 2.23–4.13) than partially saturated THQ compounds 17–22 (cLogP = 1.56–3.02), but all quinoline derivatives are more lipophilic molecules than the doxorubicin drug (cLogP = 0.48). The relationship between the lipophilicity (cLogP) and cytotoxic effects (IC₅₀), especially in HeLa and PC3 cells, the quinolines 4–16 with greater octanol/water partition coefficients showed better IC₅₀ values in HeLa and PC3 cells, contrasting with the THQs 17–22 which displayed lower cLogP values and poor activity. Molecular docking studies of most active quinoline compounds 4,5 and 10–14 against tested cancer cell lines and KDM5A, KDM4B, KDM4A, and HER-2 proteins revealed good correlations between the IC₅₀ values exhibited by these molecules and their binding interaction strength suggesting that they could be promising selective regulators of the KDM proteins.

DNA is packaged in an octamer of histones, forming chromatin, a complex of DNA and proteins. The structural matrix of a chromosome, chromatin and its changes are now regarded as important factors in controlling gene expression, which has sparked a lot of interest in understanding genetic pathways governing various diseases, including cancer. DNA methylation in the CpG dinucleotide as a transcriptional silencing mechanism, post-translational histone modifications such as acetylation, methylation, and others that affect chromatin structure, ATP-dependent chromatin remodelling, and miRNA-mediated gene silencing are all found to be important in various types of cancer. In this review, we analyze the main alterations in gene expression, epigenetic modification patterns in cancer cells, the main modulators and inhibitors of each epigenetic mechanism, and the molecular evolution of the most representative inhibitors, all of which point to a promising future for HAT, HDAC, non-glycoside DNMT inhibitors, and domain inhibitors.