Molecular modelling, synthesis, and antimalarial potentials of curcumin analogues containing heterocyclic ring

Abstract

The molecular modelling approach was applied to a series of nineteen curcumin analogues to find the possible PfRIO2 kinase inhibitory action. A putative active site in flexible loop (S1) of PfRIO2 kinase was explored computationally to recognize the molecular basis of ligands binding. The ligands (curcumin analogues; 3a-3s) were well accommodated in the selected active site (S1) due to their higher molecular size and length. Further all these synthesized compounds (3a-3s) were evaluated for their in vitro antimalarial activity according to the reported method. The antimalarial data showed that all these compounds to have parasiticidal activity with minimum killing concentrations (MKCs) range between 3.87 and 25.35 lM and schizonticidal activity with IC 50 range between 1.48 and 23.09 lM. The compound 3p showed the most significant result with maximum schizonticidal (IC 50 ; 1.48 ± 0.10 lM) and parasiticidal activities (MKC; 3.87 ± 0.36 lM) could be identified as promising lead for further investigations. ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

“…Belaji et al reported the molecular modelling, synthesis, and antimalarial potentials of curcumin analogues containing pyrazole ring. The compound 485 showed the most significant result, with maximum schizonticidal (IC 50 = 1.48 μM) and parasiticidal activities (MKC; 3.87 = μM) [ 379 ].…”

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

“…In combination with their favorable drug-like properties, privileged structures or scaffolds are widely used in rational drug design to find new lead compounds or drug candidates [1,2,3]. Pyrazole derivatives represent one of the most active classes of compounds that possess a wide spectrum of biological activities, including antibacterial and antifungal [4,5], antitumor [6,7], anti-inflammatory and analgesic [8,9], antitubercular [10], antiviral [11,12], anti-Alzheimer’s [13,14], α-glucosidase inhibitory [15], anti-diabetic [16], antileishmanial [17,18], anti-malarial [19], radioimaging [20], acaricidal and insecticidal [21,22] activities. As a privileged scaffold, pyrazole has been recently widely used in the design of anticancer agents for a multiple of tumor targets [23].…”

Molecular modeling piloted analysis for semicarbazone derivative of curcumin as a potent Abl-kinase inhibitor targeting colon cancer

“…Furthermore, the group investigated Curcumin semicarbazones anti-proliferative and antioxidant activity; and identified that semicarbazones electronwithdrawing group as well as imine carbonyl and phenoxyl radical impart curcumin semicarbazone its anti-oxidant potential (Dutta et al 2005). Furthermore, the compound has been tested for its anti-inflammatory, antinociceptive, cyclooxygenase-2 inhibition, carbonic-anhydrase inhibition, and anti-malarial (Ahmed et al 2018a, b) (Ahmed et al 2018a, b-2) (Balaji et al 2019). To assess its cytotoxic potency and assert the claims put forth by the in silico analysis, the ligands were screened via SRB assay in human CRC cell line HCT 116 and semicarbazide curcumin indicated a sevenfold better activity than curcumin and also comparable dose-dependent cell viability at lower concentrations when compared to Doxorubicin (Table 5 and Fig.…”