“…The indole chalcones given in Fig. 2 are also obeying the aforementioned rules and show excellent DLM properties ( Ramesh et al, 2020 ). Fig.…”
Section: Discussionmentioning
confidence: 79%
“…(2018). The synthesis and characterization of indole chalcones were published already by us and the synthetic procedure is available in the literature ( Ramesh et al, 2020 ).…”
Section: Methodsmentioning
confidence: 99%
“…In this study, we have taken 23 natural flavonoids and 25 anti-tubercularly active synthetic indole chalcones ( Ramesh et al, 2020 ) and studied in silico for their potential anti-SARS-CoV-2 activity along with their physicochemical and absorption, distribution, metabolism, excretion, toxicity (ADMET) properties.…”
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is distinctly infective and there is an ongoing effort to find a cure for this pandemic. Flavonoids exist in many diets as well as in traditional medicine, and their modern subset, indole-chalcones, are effective in fighting various diseases. Hence, these flavonoids and structurally similar indole chalcones derivatives were studied
in silico
for their pharmacokinetic properties including absorption, distribution, metabolism, excretion, toxicity (ADMET) and anti-SARS-CoV-2 properties against their proteins, namely, RNA dependent RNA polymerase (rdrp), main protease (M
pro
) and Spike (S) protein via homology modelling and docking. Interactions were studied with respect to biology and function of SARS-CoV-2 proteins for activity. Functional/structural roles of amino acid residues of SARS-CoV-2 proteins and, the effect of flavonoid and indole chalcone interactions which may cause disease suppression are discussed. The results reveal that out of 23 natural flavonoids and 25 synthetic indole chalcones, 30 compounds are capable of M
pro
deactivation as well as potentially lowering the efficiency of M
pro
function. Cyanidin may inhibit RNA polymerase function and, Quercetin is found to block interaction sites on the viral spike. These results suggest flavonoids and their modern pharmaceutical cousins, indole chalcones are capable of fighting SARS-CoV-2. The
in vitro
anti-SARS-CoV-2 activity of these 30 compounds needs to be studied further for complete understanding and confirmation of their inhibitory potential.
“…The indole chalcones given in Fig. 2 are also obeying the aforementioned rules and show excellent DLM properties ( Ramesh et al, 2020 ). Fig.…”
Section: Discussionmentioning
confidence: 79%
“…(2018). The synthesis and characterization of indole chalcones were published already by us and the synthetic procedure is available in the literature ( Ramesh et al, 2020 ).…”
Section: Methodsmentioning
confidence: 99%
“…In this study, we have taken 23 natural flavonoids and 25 anti-tubercularly active synthetic indole chalcones ( Ramesh et al, 2020 ) and studied in silico for their potential anti-SARS-CoV-2 activity along with their physicochemical and absorption, distribution, metabolism, excretion, toxicity (ADMET) properties.…”
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is distinctly infective and there is an ongoing effort to find a cure for this pandemic. Flavonoids exist in many diets as well as in traditional medicine, and their modern subset, indole-chalcones, are effective in fighting various diseases. Hence, these flavonoids and structurally similar indole chalcones derivatives were studied
in silico
for their pharmacokinetic properties including absorption, distribution, metabolism, excretion, toxicity (ADMET) and anti-SARS-CoV-2 properties against their proteins, namely, RNA dependent RNA polymerase (rdrp), main protease (M
pro
) and Spike (S) protein via homology modelling and docking. Interactions were studied with respect to biology and function of SARS-CoV-2 proteins for activity. Functional/structural roles of amino acid residues of SARS-CoV-2 proteins and, the effect of flavonoid and indole chalcone interactions which may cause disease suppression are discussed. The results reveal that out of 23 natural flavonoids and 25 synthetic indole chalcones, 30 compounds are capable of M
pro
deactivation as well as potentially lowering the efficiency of M
pro
function. Cyanidin may inhibit RNA polymerase function and, Quercetin is found to block interaction sites on the viral spike. These results suggest flavonoids and their modern pharmaceutical cousins, indole chalcones are capable of fighting SARS-CoV-2. The
in vitro
anti-SARS-CoV-2 activity of these 30 compounds needs to be studied further for complete understanding and confirmation of their inhibitory potential.
“…The source of our core molecule was commercially available 6-aminouracil, selected along with previously synthesized indole chalcones. [44] The structural choices behind the selection are as follows: The indole chalcones were previously synthesized and evaluated as efficient against Tb, [44] which is coinfectious with These compounds can also be more selective and less toxic in the absence of excessive functional groups. The rigidity of the compounds was also kept in mind to limit conformations and increase target selectivity.…”
Pyrido[2,3‐d]pyrimidine‐2,4(1H,3H)‐diones were synthesized, for the first time, from indole chalcones and 6‐aminouracil, and their ability to inhibit leishmaniasis and tuberculosis (Tb) infections was evaluated. The in vitro antileishmanial activity against promastigotes of Leishmania donovani revealed exceptional activities of compounds 3, 12 and 13, with IC50 values ranging from 10.23 ± 1.50 to 15.58 ± 1.67 µg/ml, which is better than the IC50 value of the standard drug pentostam of 500 μg/ml. The selectivity of the compounds towards Leishmania parasites was evaluated via ex vivo studies in Swiss albino mice. The efficiency of these compounds against Tb infection was then evaluated using the in vitro anti‐Tb microplate Alamar Blue assay. Five compounds, 3, 7, 8, 9 and 12, showed MIC100 values against the Mycobacterium tuberculosis H37Rv strain at 25 µg/ml, and compound 20 yielded an MIC100 value of 50 µg/ml. Molecular modelling of these compounds highlighted interactions with binding sites of dihydrofolate reductase, pteridine reductase and thymidylate kinase, thus establishing the rationale of their pharmacological activity against both pathogens, which is consistent with the in vitro results. From the above results, it is clear that compounds 3 and 12 are promising lead candidates for Leishmania and Mycobacterium infections and may be promising for coinfections.
“…[ 1,2 ] They are α,β‐unsaturated structures (i.e., Michael acceptors) and also are precursors in the synthesis of various heterocyclic compounds. [ 3–5 ] Chalcones have presented a broad spectrum of biological activities such as antibacterial, [ 6 ] antifungal, [ 7 ] antitubercular, [ 8,9 ] anti‐inflammatory, [ 10 ] antimalarial, [ 11 ] and antitumor, [ 12 ] among others. It is believed that the presence of the double bond in conjugation with the carbonyl functionality is the main property responsible for the biological activities observed in chalcones.…”
A novel series of quinoline‐based symmetrical and unsymmetrical bis‐chalcones was synthesized via a Claisen–Schmidt condensation reaction between 3‐formyl‐quinoline/quinolone derivatives with acetone or arylidene acetones, respectively, by using KOH/MeOH/H2O as a reaction medium. Twelve of the obtained compounds were evaluated for their in vitro cytotoxic activity against 60 different human cancer cell lines according to the National Cancer Institute protocol. Among the screened compounds, the symmetrical N‐butyl bis‐quinolinyl‐chalcone 14g and the unsymmetrical quinolinyl‐bis‐chalcone 17o bearing a 7‐chloro‐substitution on the N‐benzylquinoline moiety and 4‐hydroxy‐3‐methoxy substituent on the phenyl ring, respectively, exhibited the highest overall cytotoxicity against the evaluated cell lines with a GI50 range of 0.16–5.45 µM, with HCT‐116 (GI50 = 0.16) and HT29 (GI50 = 0.42 μM) (colon cancer) representing best‐case scenarios. Notably, several GI50 values for these compounds were lower than those of the reference drugs doxorubicin and 5‐FU. Docking studies performed on selected derivatives yielded very good binding energies in the active site of proteins that participate in key carcinogenic pathways.
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