Arch Pharm Chem Life Sci. 2019;e1900079. wileyonlinelibrary.com/journal/ardp © 2019 Deutsche Pharmazeutische Gesellschaft | 1 of 13 https://doi.org/10.1002/ardp.201900079 Received: 26 March 2019 | Revised: 14 August 2019 | Accepted: 1 September 2019 DOI: 10.1002/ardp.201900079 FULL PAPER Synthesis of thiazolyl hydrazonothiazolamines and 1,3,4‐thiadiazinyl hydrazonothiazolamines as a class of antimalarial agents Kodam Sujatha 1 | Naidu Babu Ommi 2 | Anwita Mudiraj 2 | Phanithi Prakash Babu 2 | Rajeswar Rao Vedula 1 1 Department of Chemistry, National Institute of Technology, Warangal, Telangana, India 2 Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India Correspondence Phanithi Prakash Babu, Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana 500046, India. Email: prakash@uohyd.ac.in Rajeswar Rao Vedula, Department of Chemistry, National Institute of Technology, Warangal, Telangana 506004, India. Email: rajeswarnitw@gmail.com Abstract Novel thiazolyl hydrazonothiazolamines and 1,3,4‐thiadiazinyl hydrazonothiazola- mines were synthesized by a facile one‐pot multicomponent approach by the reaction of 2‐amino‐4‐methyl‐5‐acetylthiazole, thiosemicarbazide or thiocarbohydrazide and phenacyl bromides or 3‐(2‐bromoacetyl)‐2H‐chromen‐2‐ones in acetic acid with good to excellent yields. These new compounds were screened in vitro for their antimalarial activity; among them, four compounds, 4h, 4i, 4k, 4l, showed moderate activity with half‐maximal inhibitory concentration (IC 50 ) values of 3.2, 2.7, 2.7, and 2.8 and 3.2, 3.2, 3.1, and 3.5 μM against chloroquine‐sensitive and ‐resistant strains of Plasmodium falciparum, respectively. Compound 4l inhibited the ring stage growth of P. falciparum 3D7 at an IC 90 concentration of 12.5 μM in a stage‐specific assay method, where the culture is incubated with specific stages of P. falciparum for 12 hr, and no activity was found against the trophozoite and schizont stages, confirming that 4l may have potent action against the ring stage of P. falciparum. KEYWORDS 2‐amino‐4‐methyl‐5‐acetylthiazole, antimalarial activity, bithiazoles, multicomponent reactions, thiazolothiadiazines 1 | INTRODUCTION Malaria is a parasitic disease transmitted to humans by the female Anopheles mosquito and continues to remain a lethal infectious disease. According to WHO 2017 report, [1] an estimated 216 million cases of malaria occurred worldwide in 2016, and India accounts for 6% of it. Plasmodium falciparum, the most virulent species of this parasite has developed resistance to most available antimalarial drugs. This has been a constant challenge to malaria control initiatives necessitating the search for novel and structurally diverse antimalarial drugs as a viable strategy to combat this issue. Multicomponent reactions (MCRs) are modern methods for the synthesis of drug molecules. [2] The advantages of MCRs are convergent, one pot and sequential assembling of starting materials to get the final product in a short time. MCRs play a vital role in modern organic synthesis. MCRs are good synthetic approaches for functionalized heterocyclic compounds without any side products. [3,4] Thiazole scaffolds (Figure 1) are found in many natural products [5] and possess diverse medicinal and pharmaceutical applications such as antitubercular, [6,7] anticonvulsant, [8] anticancer, [9] antiviral, [10] antimi- crobial, [11] antimalarial [12] and anti‐inflammatory activity. [13] Coumarin is an important pharmacophore having many applica- tions in the fields of medicinal chemistry as well as pharmaceuticals like antifungal, [14] anti‐HIV agents, [15] anti‐Alzheimers [16] and also acts as a luminescent material. [17] When the coumarin ring is attached with the thiazole ring, it exhibits improved biological activities like being an anti‐inflammatory and anti‐analgesic agent. [18] On the other hand, thia- diazines are also versatile biologically important heterocyclic mole- cules [19] with proven applications as antidepressant, [20] antihyperten- sive [21] and antiproliferative agents. [22]