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.
Review
Public, Environmental & Occupational Health
G. Dennis Shanks
Summary: Since their first use in the 1920s, 8-aminoquinolines have been known to have important toxicities. However, when combined with other antimalarial drugs, particularly quinine or chloroquine, they can enhance efficacy and reduce toxicity.
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
(2022)
Review
Medicine, Research & Experimental
Roberto Barbosa Bazotte, Sandro Massao Hirabara, Tamires Afonso Duarte Serdan, Raquel Bragante Gritte, Talita Souza-Siqueira, Renata Gorjao, Laureane Nunes Masi, Marina Masetto Antunes, Vinicius Cruzat, Tania Cristina Pithon-Curi, Rui Curi
Summary: Quinine, originally extracted from the bark of Chinchona trees, has been used for treating fever since the seventeenth century. Compounds derived from quinine, such as chloroquine and hydroxychloroquine, are being studied worldwide for treating COVID-19, with some discrepancies in clinical trial outcomes. The potential underlying molecular mechanisms of how CQ and HCQ inhibit viral replication may lead to the development of novel drugs to combat COVID-19.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Junli Chen, Adrian P. Campbell, Laurence P. G. Wakelin, Angela M. Finch
Summary: The study investigated the allosteric activity of bis(4-aminoquinoline) compounds on the α(1A) adrenoceptor, showing their ability as allosteric modulators and the optimal linker length requirement between 7 and 11 methylene units.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Katarina Komatovic, Ana Matosevic, Natasa Terzic-Jovanovic, Suzana Zunec, Sandra Segan, Mario Zlatovic, Nikola Marakovic, Anita Bosak, Dejan M. Opsenica
Summary: This study investigated the inhibitory activity of 22 structurally distinct 4-aminoquinolines bearing an adamantane moiety on AChE and BChE, and their ability to cross the BBB. Compound 5 and compound 8 showed the best inhibition and potential as structural scaffolds for designing novel central nervous system drugs.
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
Yu-Chieh Wu, Meng-Tien Lu, Po-Chen Chu, Chih-Shiang Chang
Summary: In this study, multiple derivatives of 4-aminoquinoline containing heterocyclic rings were synthesized and their effects on the HIF-1 alpha signaling pathway were evaluated. Compound 3s, identified as the most promising HIF-1 alpha inhibitor, showed exceptional antiproliferative effects and inhibited HIF-1 alpha expression by decreasing the level of HIF-1 alpha mRNA.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Mieke Guinan, Ningwu Huang, Chris S. Hawes, Marcelo A. Lima, Mark Smith, Gavin J. Miller
Summary: Analogues of canonical nucleosides play crucial roles in antiviral and anticancer research, with 4'-thionucleosides being an important chemotype in this field. Synthetic capability towards a common 4-thioribose building block is established, allowing access to thio-ribo and thio-arabino pyrimidine nucleosides, as well as their 4'-sulfinyl derivatives. These new analogues exhibit varying cytotoxic capabilities against human pancreatic cancer and human primary glioblastoma cell lines, with reasons for their reduced activity compared to established nucleoside analogues still unclear. This access to chemotypes with thiohemiaminal linkages will enable further exploration in purine and triphosphate analogues for potential resistance towards relevant hydrolytic enzymes in nucleic acid biochemistries.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Fei Chen, Huidan Geng, Chun Li, Jianta Wang, Bing Guo, Lei Tang, Yuan-Yong Yang
Summary: In this study, an atom and step economic procedure was developed for the preparation of 4-aminoquinolines based on an aerobic dehydrogenative aromatization strategy. The synergistic Pd/Cu catalysis played a crucial role in the coupling reaction between aromatic/aliphatic amines and 2,3-dihydroquinolin-4(1H)-ones, resulting in moderate to high yields of the desired products. Moreover, the application of this methodology for the preparation and late-stage diversification of marketed drugs was demonstrated.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Rachael N. Magwaza, Muna Abubaker, Buthaina Hussain, Michael Haley, Kevin Couper, Sally Freeman, Niroshini J. Nirmalan
Summary: The emergence of drug-resistant malaria requires the development of new therapies. A study identified a novel quinoline compound with high antimalarial activity, particularly against the ring stages of the parasite lifecycle. The compound showed synergistic activity when combined with artemether and maintained activity against different strains of the parasite, suggesting no cross-resistance.
Article
Chemistry, Multidisciplinary
Yosuke Hisamatsu, Fangzhou Cheng, Katsuhiro Yamamoto, Hiroshi Takase, Naoki Umezawa, Tsunehiko Higuchi
Summary: In this study, a new amphiphilic 4-aminoquinoline (4-AQ)-tetraphenylethene (TPE) conjugate was reported, which exhibited kinetically controllable stepwise self-assembly and the ability to switch its kinetic nature in response to pH. The self-assembly process of the 4-AQ amphiphile involved the formation of sphere-like nanoparticles, a transition to short nanofibers, and their growth to long nanofibers at room temperature. The time scale of the self-assembly process varied depending on the pH-responsiveness of the 4-AQ moiety.
Article
Biotechnology & Applied Microbiology
Ayesha Aktar Khanam Choudhury, Sathishkumar Vinayagam, Nayana Adhikari, Surajit Kumar Ghosh, Kamaraj Sattu
Summary: Antimalarial drug resistance is a major problem, and a new class of Pf-DHFR inhibitors has been developed to address this issue. In vitro experiments showed that these inhibitors have good antimalarial activity with no toxicity to fibroblast cell lines.
Article
Chemistry, Organic
Hetal Soni, Navin B. Patel, Rahul B. Parmar, Manuel J. Chan-Bacab, Gildardo Rivera
Summary: This study aims to synthesize thiazolidine-4-one compounds with a pyrimidine nucleus using microwave irradiation to save time and energy. The synthesized compounds showed excellent biological activities against bacteria, fungi, tuberculosis, malaria parasites, and protozoa.
LETTERS IN ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Navin B. Patel, Hetal I. Soni, Rahul B. Parmar, Manuel J. Chan-Bacab, Gildardo Rivera
Summary: Triazoles and pyrimidines are bioactive molecules, and the synthesized compounds showed antibacterial, antifungal, anti-tuberculosis, antimalarial, and anti-protozoal activities. The new compounds demonstrate bioactive responses and are synthesized using simple methods.
LETTERS IN ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Aparna Bahuguna, Diwan S. Rawat
MEDICINAL RESEARCH REVIEWS
(2020)
Article
Chemistry, Physical
Gunjan Purohit, Diwan S. Rawat, Oliver Reiser
Article
Chemistry, Organic
Kamlesh Kumar, Prashant Kumar, Penny Joshi, Diwan S. Rawat
TETRAHEDRON LETTERS
(2020)
Article
Chemistry, Physical
U. Chinna Rajesh, Yaroslav Losovyj, Chun-Hsing Chen, Jeffrey M. Zaleski
Article
Microbiology
Garima Arora, Gagandeep, Assirbad Behura, Tannu Priya Gosain, Ravi P. Shaliwal, Saqib Kidwai, Padam Singh, Shamseer Kulangara Kandi, Rohan Dhiman, Diwan S. Rawat, Ramandeep Singh
FRONTIERS IN MICROBIOLOGY
(2020)
Article
Chemistry, Physical
Upasana Gulati, U. Chinna Rajesh, Diwan S. Rawat
Article
Chemistry, Multidisciplinary
Gunjan Purohit, Aneeta Kharkwal, Diwan S. Rawat
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2020)
Article
Chemistry, Organic
Upasana Gulati, U. Chinna Rajesh, Diwan S. Rawat
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Gagandeep, Prince Kumar, Shamseer Kulangara Kandi, Kasturi Mukhopadhyay, Diwan S. Rawat
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Medicine, General & Internal
Vallabh Suresh, Kaleb Byers, Ummadisetti Chinna Rajesh, Francesco Caiazza, Gina Zhu, Charles S. Craik, Kimberly Kirkwood, Vincent Jo Davisson, Daniel A. Sheik
Summary: The gastricsin activity assay developed in this study offers a rapid and accurate method for distinguishing between mucinous and non-mucinous pancreatic cyst fluids. The assay shows improvements in differentiation compared to standard ELISA assays and has a minimal impact on standard clinical care.
Article
Chemistry, Multidisciplinary
Upasana Gulati, U. Chinna Rajesh, Diwan S. Rawat, Jeffrey M. Zaleski
Article
Chemistry, Multidisciplinary
Prince Kumar, Shamseer Kulangara Kandi, Sunny Manohar, Kasturi Mukhopadhyay, Diwan S. Rawat