Exploring diverse frontiers: Advancements of bioactive 4-aminoquinoline-based molecular hybrids in targeted therapeutics and beyond.

Amongst heterocyclic compounds, quinoline and its derivatives are advantaged scaffolds that appear as a significant assembly motif for developing new drug entities. Aminoquinoline moiety has gained significant attention among researchers in the 21stcentury. Considering the biological and pharmaceutical importance of aminoquinoline derivatives, herein, we review the recent developments (since 2019) in various biological activities of the 4-aminoquinoline scaffold hybridized with diverse heterocyclic moieties such as quinoline, pyridine, pyrimidine, triazine, dioxine, piperazine, pyrazoline, piperidine, imidazole, indole, oxadiazole, carbazole, dioxole, thiazole, benzothiazole, pyrazole, phthalimide, adamantane, benzochromene, and pyridinone. Moreover, by gaining knowledge about SARs, structural insights, and molecular targets, this review may help medicinal chemists design cost-effective, selective, safe, and more potent 4-aminoquinoline hybrids for diverse biological activities.

Triazole hybrid compounds: A new frontier in malaria treatment.

Reviewing the advancements in malaria treatment, the emergence of triazole hybrid compounds stands out as a groundbreaking development. Combining the advantages of triazole and other moieties, these hybrid compounds offer a new frontier in the battle against malaria. Their potential as effective antimalarial agents has captured the attention of researchers and holds promise for overcoming the challenges posed by drug-resistant malaria strains. We focused on their broad spectrum of antimalarial activity of diverse hybridized 1,2,3-triazoles and 1,2,4-triazoles, structure-activity relationship (SAR), drug-likeness, bioavailability and pharmacokinetic properties reported since 2018 targeting multiple stages of the Plasmodium life cycle. This versatility makes them highly effective against both drug-sensitive and drug-resistant strains of P. falciparum, making them invaluable tools in regions where resistance is prevalent. The synergistic effects of combining the triazole moiety with other pharmacophores have resulted in even greater antimalarial potency. This approach has the potential to circumvent existing resistance mechanisms and provide a more sustainable solution to malaria treatment. While triazole hybrid compounds show great promise, further research and clinical trials are warranted to fully evaluate their safety, efficacy and long-term effects. As research progresses, these compounds can potentially revolutionize the field and contribute to global efforts to eradicate malaria, ultimately saving countless lives worldwide.

Recent developments in antimalarial activities of 4-aminoquinoline derivatives.

Malaria is the fifth most lethal parasitic infection in the world. Antimalarial medications have played a crucial role in preventing and eradicating malaria. Numerous heterocyclic moieties have been incorporated into the creation of effective antimalarial drugs. The 4-aminoquinoline moiety is favoured in antimalarial drug discovery due to the diverse biological applications of its derivative. Since the 1960s, 4-aminoquinoline has been an important antimalarial drug due to its low toxicity, high tolerability, and rapid absorption after administration. This review focused on the antimalarial efficacy of the 4-aminoquinoline moiety hybridised with various heterocyclic scaffolds developed by scientists since 2018 against diverse Plasmodium clones. It could aid in the future development of more effective antimalarial agents.

Pyrazole and pyrazoline derivatives as antimalarial agents: A key review.

Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the development of drug resistance in malaria parasites. The standard treatment for malaria is artemisinin-combination therapy (ACT). Nevertheless, the Plasmodium parasite's extensive resistance to prior drugs and reduced ACT efficiency necessitates novel drug discovery. The progress in discovering novel, affordable, and effective antimalarial agents is significant in combating drug resistance, and the hybrid drug concept can be used to covalently link two or more active pharmacophores that may act on multiple targets. Pyrazole and pyrazoline derivatives are considered pharmacologically necessary active heterocyclic scaffolds that possess almost all types of pharmacological activities. This review summarized recent progress in antimalarial activities of synthesized pyrazole and pyrazoline derivatives. The studies published since 2000 are included in this systematic review. This review is anticipated to be beneficial for future study and new ideas in searching for rational development strategies for more effective pyrazole and pyrazoline derivatives as antimalarial drugs.

Antibacterial activities with the structure-activity relationship of coumarin derivatives.

The development of drug-resistant bacteria, as well as multidrug-resistant pathogens related to substantial mortality, is an important global health threat. The wide range of biological activities and the wealthy use of coumarin-containing drugs in the clinic have encouraged more and more interest in this class of heterocycles. Various coumarin-based antibiotic hybrids have been developed in the last decade and most of them exhibited potential antibacterial potency. This present review summarizes the current innovations of coumarin-based derivatives with potential antibacterial activities against a variety of Gram-negative and Gram-positive bacteria discussing various aspects of structure-activity relationship (SAR). The improved SAR will provide further insight into the rational improvement of coumarin hybrids with astounding strength against multidrug-resistant bacteria.

The significance of N-methylpicolinamides in the development of anticancer therapeutics: Synthesis and structure-activity relationship (SAR) studies.

Cancer is the second most important cause of death worldwide. There is always a demand for new anticancer drugs and continuously a wide variety of natural and synthetic compounds were developed by the researchers. Nowadays, a large number of drugs in clinical practice were found to have a high incidence of side effect and multidrug conflict. The development of novel less toxic, low cost and very energetic N-methylpicolinamide-bearing hybrids is a hot research topic in the community of medicinal chemistry. Herein we highlight the current advances in the synthesis of picolinamide-containing heterocyclic compounds as potent anticancer agents. In addition, briefly explore their structure-activity relationship studies for the inspiration of the innovation and development of more potent and effective drugs against various death-causing cancer diseases.

Aryl fluorosulfate analogues as potent antimicrobial agents: SAR, cytotoxicity and docking studies.

A series of aryl fluorosulfate analogues (1-37) were synthesized and tested for in vitro antibacterial and antifungal studies, and validated by docking studies. The compounds 9, 12, 14, 19, 25, 26, 35, 36 and 37 exhibited superior antibacterial potency against tested bacterial strains, while compounds 2, 4, 5, 15, 35, 36 and 37 were found to have better antifungal activity against tested fungal strains, compared to standard antibiotic gentamicin and ketoconazole respectively. Among all the synthesized 37 analogs, compounds 25, 26, 35, 36 and 37 displayed excellent anti-biofilm property against Staphylococcus aureus. The structure-activity relationship (SAR) revealed that the antimicrobial activity depends upon the presence of -OSO2F group and slender effect of different substituent's on the phenyl rings. The electron donating (OCH3) groups in analogs increase the antibacterial activity, and interestingly the electron withdrawing (Cl, NO2, F and Br) groups increase the antifungal activity (except compound 35, 36 and 37). The mechanism of potent compounds showed membrane damage on bacteria confirmed by SEM. Compounds 35, 36 and 37 exhibited highest glide g-scores in molecular docking studies and validated the biocidal property.