Review
Chemistry, Medicinal
Lekkala Ravindar, Siti Aishah Hasbullah, K. P. Rakesh, Nurul Izzaty Hassan
Summary: Malaria is a deadly parasitic infection ranked as the fifth most lethal worldwide. Antimalarial medications are crucial for preventing and eradicating malaria. The 4-aminoquinoline moiety has diverse biological applications and has been favored in antimalarial drug discovery. This review focuses on its efficacy when hybridized with various heterocyclic scaffolds, aiding the development of more effective antimalarial agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Mohd Asyraf Shamsuddin, Amatul Hamizah Ali, Nur Hanis Zakaria, Mohd Fazli Mohammat, Ahmad Sazali Hamzah, Zurina Shaameri, Kok Wai Lam, Wun Fui Mark-Lee, Hani Kartini Agustar, Mohd Ridzuan Mohd Abd Razak, Jalifah Latip, Nurul Izzaty Hassan
Summary: The study synthesized a new series of hybrids, among which 4b demonstrated strong antiplasmodial activity against both 3D7 and K1 strains with low cytotoxic effect. It displayed high selectivity index and low resistance index, suggesting selective inhibition on the 3D7 and K1 strains. Additionally, molecular docking analysis indicated that P. falciparum lactate dehydrogenase could be a potential molecular target for compound 4b.
Article
Chemistry, Medicinal
Shefali Chowdhary, Shalini, Joel Mosnier, Isabelle Fonta, Bruno Pradines, Nosipho Cele, Pule Seboletswe, Parvesh Singh, Vipan Kumar
Summary: In the search for new antimalarial agents, a multitargeted approach was used to synthesize triazolopyrimidine- and 4-aminoquinolines-based hybrids. In vitro evaluation showed that these hybrids exhibited strong antimalarial activity, outperforming existing compounds. Mechanistic studies validated the inhibitory effects of these active compounds on the parasite, and also identified their target sites.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Jufrizal Syahri, Rahmiwati Hilma, Amatul Hamizah Ali, Norzila Ismail, Ng Yee Ling, Nurlaili, Beta Achromi Nurohmah, Hani Kartini Agustar, Lau Yee Ling, Jalifah Latip
Summary: This study synthesized chalcone derivatives and evaluated their antimalarial properties against Plasmodium parasites. Docking analysis revealed the potential molecular target of these compounds. The synthesized chalcone derivatives showed promising antimalarial activities and low cross-resistance with existing drugs.
Review
Chemistry, Medicinal
Eslam R. El-Sawy, Gilbert Kirsch
Summary: Marine products, particularly aplysinopsins, are valuable sources of biologically active compounds. Aplysinopsins, derived from various marine organisms such as sponges, corals, sea anemone, and nudibranch, have been isolated from different geographic regions including the Pacific, Indonesia, Caribbean, and Mediterranean. This review provides an up-to-date overview of the sources, synthesis, and biological activities of aplysinopsin derivatives.
Article
Chemistry, Medicinal
Satoshi Mizuta, Farhana Mosaddeque, Mya Myat Ngwe Tun, Awet Alem Teklemichael, Mayumi Taniguchi, Masashi Hosokawa, Tomoko Yamaguchi, Juliann Makau, Nguyen Tien Huy, Shusaku Mizukami, Noriyuki Nishida, Kouichi Morita, Kenji Hirayama
Summary: We have modified the terminal amino group of N-1-(7-chloroquinolin-4-yl) butane-1,4-diamine to synthesize a series of 7-chloro-4-aminoquinoline derivatives and evaluated their potential as anti-malarial and anti-viral agents. Some of these compounds showed promising anti-malarial effects against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. In addition, they were tested in vitro against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compound 5h, which contained an N-mesityl thiourea group, exhibited significant anti-infectious effects against malaria, IAV, and SARS-CoV-2. These findings provide new insights for the discovery of drugs for malaria prevention and treatment, as well as virus co-infection.
Article
Medicine, Research & Experimental
Nicolas Glanzmann, Luciana Maria Ribeiro Antinarelli, Isabelle Karine da Costa Nunes, Henrique Marcelo Gualberto Pereira, Eduardo Antonio Ferraz Coelho, Elaine Soares Coimbra, Adilson David da Silva
Summary: Quinoline and 1,2,3-triazoles are nitrogen-based heterocycles with diverse pharmacological properties. In this study, derivatives from 4-aminoquinoline and 1,2,3-triazole showed promising antileishmanial activity, especially compound 4, which exhibited a multi-target action on Leishmania parasites and selective toxicity. Further research on derivative 4 is recommended for potential treatment against leishmaniasis.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Medicinal
A. Dassonville-Klimpt, J. Schneider, C. Damiani, C. Tisnerat, A. Cohen, N. Azas, M. Marchivie, J. Guillon, C. Mullie, P. Agnamey, Anne Totet, J. Dormoi, N. Taudon, B. Pradines, P. Sonnet
Summary: This study designed, synthesized, and evaluated five new series of aminoalcohol quinolines against Pf3D7 and PfW2 strains in vitro. Among the compounds, fourteen showed promising activity with IC50 values below or near 50.0 nM and high selectivity index. Compound 17b exhibited potent antimalarial activity with IC50 values of 14.9 nM and 11.0 nM against Pf3D7 and PfW2, respectively, and a high selectivity index. Further experiments and in vivo studies are needed to confirm its safety and efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Shiyang Zhou, Gangliang Huang
Summary: Marine alkaloids exhibit activity in antifungal and antimalarial properties. The discussion covers the optimization process, chemical synthesis, antimalarial activity, and antibacterial activity of various compounds.
CHEMICAL BIOLOGY & DRUG DESIGN
(2021)
Article
Biochemistry & Molecular Biology
Anu Saini, Sumit Kumar, Raghu Raj, Shefali Chowdhary, Mathieu Gendrot, Joel Mosnier, Isabelle Fonta, Bruno Pradines, Vipan Kumar
Summary: A library of 1H-1,2,3-triazole-tethered 4-aminoquinoline-benzoxaborole hybrids was synthesized and screened for anti-plasmodial efficacy, with the inclusion of quinoline core resulting in enhanced activities. The most potent conjugate exhibited lower cross resistance with Chloroquine against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 strains of P. falciparum.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Rattanaporn Wansri, Aye Chan Khine Lin, Jutharat Pengon, Sumalee Kamchonwongpaisan, Nitipol Srimongkolpithak, Roonglawan Rattanajak, Patcharin Wilasluck, Peerapon Deetanya, Kittikhun Wangkanont, Kowit Hengphasatporn, Yasuteru Shigeta, Jatupol Liangsakul, Aphinya Suroengrit, Siwaporn Boonyasuppayakorn, Taksina Chuanasa, Wanchai De-Eknamkul, Supot Hannongbua, Thanyada Rungrotmongkol, Supakarn Chamni
Summary: In this study, N-aryl amide piperine analogs were prepared and evaluated for their antitrypanosomal, antimalarial, and anti-SARS-CoV-2 main protease activities. Compound 5 exhibited the most robust biological activities with no cytotoxicity against mammalian cell lines. It showed higher inhibitory activities against trypanosomiasis, malaria, and SARS-CoV-2 main protease compared to piperine.
Article
Chemistry, Multidisciplinary
Varsha Sharma, Praveena Mishra, Arun Sharma, Rupali Dutt, Virendra Shankhwar, Pooja Prajapati, Sakshi Shrivastava, Dau Dayal Agarwal
Summary: This study achieved insights into a multicomponent cyclocondensation reaction, synthesizing a novel compound in a shorter time using Ni-Cu-Al-CO3 hydrotalcite as a heterogeneous catalyst. The hydrotalcite exhibited efficient and versatile catalytic properties, making it environmentally friendly and recyclable. The synthesized product showed antimicrobial activity and displayed potential antibacterial activity against human pathogens.
Article
Chemistry, Multidisciplinary
Vinay Shankar Tiwari, Prince Joshi, Kanchan Yadav, Anamika Sharma, Sushobhan Chowdhury, Ashan Manhas, Niti Kumar, Renu Tripathi, Wahajul Haq
Summary: A series of novel 4-aminoquinoline analogues with a methyl group were synthesized and evaluated for their antimalarial activity, showing good potential in inhibiting Plasmodium falciparum with low toxicity levels. The introduction of a 4-methylamino substitution is well tolerated and holds promise for the discovery of new antimalarial agents against drug-resistant malaria.
Article
Chemistry, Multidisciplinary
Youzhi Li, Anthony Loureiro, Michel Nguyen, Marion Laurent, Christian Bijani, Francoise Benoit-Vical, Anne Robert, Yan Liu, Bernard Meunier
Summary: In response to the urgent need for new efficient drugs to combat the spreading resistance of malaria parasite Plasmodium falciparum to artemisinin-based combination therapies, a series of novel hybrid drugs named Atokels were synthesized and characterized. These drugs, based on an 8-amino- or 8-hydroxyquinoline entity covalently bound to a 1,4-naphthoquinone through a polyamine linker, have been designed to target the parasite mitochondrion and induce damaging oxidative stress. Promising antimalarial activity was shown by the most effective Atokel drug on an artemisinin-resistant P. falciparum strain, with no cytotoxicity at 50 μm.
Article
Chemistry, Multidisciplinary
Tadewos Damena, Mamaru Bitew Alem, Digafie Zeleke, Tegene Desalegn, Rajalakshmanan Eswaramoorthy, Taye B. Demissie
Summary: Interest is growing in the use of transition metal complexes for various applications. In this study, three complexes were synthesized and characterized. The results demonstrate their potential as bioactive and antioxidant agents.
FRONTIERS IN CHEMISTRY
(2022)