A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK.

Purpose: Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. Methods: The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. Results: HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Conclusion: Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.

The Synthesis of 2'-Hydroxychalcones under Ball Mill Conditions and Their Biological Activities.

Chalcones are polyphenols that belong to the flavonoids family, known for their broad pharmacological properties. They have thus attracted the attention of chemists for their obtention and potential activities. In our study, a library of compounds from 2'-hydroxychalcone's family was first synthesized. A one-step mechanochemical synthesis via Claisen-Schmidt condensation reaction under ball mill conditions was studied, first in a model reaction between a 5'-fluoro-2'-hydroxyacetophenone and 3,4-dimethoxybenzaldehyde. The reaction was optimized in terms of catalysts, ratio of reagents, reaction time, and influence of additives. Among all assays, we retained the best one, which gave the highest yield of 96% when operating in the presence of 1 + 1 eq. of substituted benzaldehyde and 2 eq. of KOH under two grinding cycles of 30 min. Thus, this protocol was adopted for the synthesis of the selected library of 2'-hydroxychalcones derivatives. The biological activities of 17 compounds were then assessed against Plasmodium falciparum, Leishmania donovani parasite development, as well as IGR-39 melanoma cell lines by inhibiting their viability and proliferation. Compounds 6 and 11 are the most potent against L. donovani, exhibiting IC50 values of 2.33 µM and 2.82 µM, respectively, better than the reference drug Miltefosine (3.66 µM). Compound 15 presented the most interesting antimalarial activity against the 3D7 strain, with IC50 = 3.21 µM. Finally, chalcone 12 gave the best result against IGR-39 melanoma cell lines, with an IC50 value of 12 µM better than the reference drug Dacarbazine (IC50 = 25 µM).

Highly oxidized rearranged derivatives of quinochalcone C-glycosides from Carthamus tinctorius.

Safflopentsides A-C (1-3), three highly oxidized rearranged derivatives of quinochalcone C-glycosides, were isolated from the safflower yellow pigments. Their structures were determined based on a detailed spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR), and the absolute configurations were confirmed by the comparison of experimental ECD spectra with calculated ECD spectra. Compounds 1-3 have an unprecedented cyclopentenone or cyclobutenolide ring A containing C-glucosyl group, respectively. The plausible biosynthetic pathways of compounds have been presented. At 10 µM, 2 showed strong inhibitory activity against rat cerebral cortical neurons damage induced by glutamate and oxygen sugar deprivation.

Design, Synthesis and In vitro Antitubercular Effect of New Chalcone Derivatives Coupled with 1,2,3-Triazoles: A Computational Docking Techniques.

A very interesting foundation for this study is the creation of new methods for modifying compounds with a 1,2,3-triazole and chalcone scaffolds, as these compounds are significant in organic synthesis, particularly in the synthesis of bioactive organic compounds. To contribute to the development of an efficient method for the conversion of antimicrobial and antituberculosis heterocyclics, a novel series of cyclohepta pyridinone fused 1,2,3-triazolyl chalcones were designed and synthesized. All the newly prepared scaffolds were characterized by FT-IR, NMR (1H & 13C) and mass spectrometry. Among the tested compounds, hybrids 8b, 8d, and 8f exhibited exceptional antibacterial susceptibilities with zone of inhibition 27.84±0.04, 32.27±0.02, and 38.26±0.01 mm against the tested E. faecalis bacteria, whereas 8d had better antitubercular potency against M. tuberculosis H37Rv strain with MIC value 5.25 µg/mL, compared to Streptomycin [MIC=5.01 µg/mL]. All the synthesized compounds were initially assessed in silico against the targeted protein i. e., DprE1 that indicated compound 8d, 8f and 8h along with several other 1,2,3-triazole compounds as possible inhibitors. Based on docking results, 8d showed that the amino acids His74(A), Lys76(A), Cys332(A), Asp331(A), Val307(A), Tyr357(A), Met226(A), Gln276(A), Gly75(A), Peo58(A), Leu259(A), and Lys309(A) exhibited highly stable binding to DprE1 receptor of Mycobacterium tuberculosis (PDB: 4G3 U). Moreover, these scaffolds physicochemical characteristics, filtration molecular properties, assessment of toxicity, and bioactivity scores were assessed in relation to ADME (absorption, distribution, metabolism, and excretion).

Pharmacokinetic study of multicomponent in Hong-Hua-Xiao-Yao tablet.

Hong-Hua-Xiao-Yao tablet (HHXYT) is attracting attention increasingly because of its use in treatment of mammary gland hyperplasia (MGH) and menopausal syndrome. However, its pharmacokinetics remains unclear. This study developed a sensitive and rapid method for simultaneous determination of 10 compounds of HHXYT in rat plasma by liquid chromatography-tandem mass spectrometry and to compare the pharmacokinetics of these compounds in MGH rats and sham operated rats. The linearity, accuracy, precision, stability and matrix effect were within acceptable ranges. This established method was successfully applied to a pharmacokinetics study of 10 compounds in sham operated and MGH rats. According to the results, the bioavailability of glycyrrhetinic acid was highest in MGH rats and sham operated rats. The mean residence times of glycyrrhetinic acid and glycyrrhetinic acid 3-O-glucuronide were higher than those of the other compounds while the mean residence time and half-life of liquiritin, isoliquiritin and paeoniflorin were lower. Some pharmacokinetic parameters of ormononetin, liquiritigenin, isoliquiritigenin, liquiritin, isoliquiritin, paeoniflorin, protocatechuic acid and senkyunolide I were significantly different between MGH rats and sham operated rats. This study elucidated the dynamic changes of multiple components in rats after oral administration of HHXYT systematically and comprehensively, which provided guidance for clinical application.

Probing the inhibition of MAO-B by chalcones: an integrated approach combining molecular docking, ADME analysis, MD simulation, and MM-PBSA calculations.

CONTEXT: Monoamine oxidase B (MAO-B), an enzyme of significant relevance in the realm of neurodegenerative disorders, has garnered considerable attention as a potential target for therapeutic intervention. Natural compounds known as chalcones have shown potential as MAO-B inhibitors. In this particular study, we employed a multimodal computational method to evaluate the inhibitory effects of chalcones on MAO-B. METHODS: Molecular docking methods were used to study and assess the complicated binding interactions that occur between chalcones and MAO-B. This extensive analysis provided a valuable and deep understanding of possible binding methods as well as the key residues implicated in the inhibition process. Furthermore, the ADME investigation gave valuable insights into the pharmacokinetic properties of chalcones. This allowed them to be assessed in terms of drug-like attributes. The use of MD simulations has benefited in the research of ligand-protein interactions' dynamic behaviour and temporal stability. MM-PBSA calculations were also done to estimate the binding free energies and acquire a better knowledge and understanding of the binding affinity between chalcones and MAO-B. Our thorough method gives a thorough knowledge of chalcones' potential as MAO-B inhibitors, which will be useful for future experimental validation and drug development efforts in the context of neurodegenerative illnesses.

Quinazoline-chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in-silico studies of potential anticancer activity against multiple myeloma.

Two new series of quinazoline-chalcone hybrids were designed, synthesized as histone deacetylase (HDAC)/epidermal growth factor receptor (EGFR) dual inhibitors, and screened in vitro against the NCI 60 human cancer cell line panel. The most potent derivative, compound 5e bearing a 3,4,5-trimethoxyphenyl chalcone moiety, showed the most effective growth inhibition value against the panel of NCI 60 human cancer cell lines. Thus, it was selected for further investigation for NCI 5 log doses. Interestingly, this trimethoxy-substituted analog inhibited the proliferation of Roswell Park Memorial Institute (RPMI)-8226 cells by 96%, at 10 µM with IC50 = 9.09 ± 0.34 µM and selectivity index = 7.19 against normal blood cells. To confirm the selectivity of this compound, it was evaluated against a panel of tyrosine kinase enzymes. Mechanistically, it successfully and selectively inhibited HDAC6, HDAC8, and EGFR with IC50 = 0.41 ± 0.015, 0.61 ± 0.027, and 0.09 ± 0.004 µM, respectively. Furthermore, the selected derivative induced apoptosis via the mitochondrial apoptotic pathway by raising the Bax/Bcl-2 ratio and activating caspases 3, 7, and 9. Also, the flow cytometry analysis of RPMI-8226 cells showed that the trimethoxy-substituted analog produced cell cycle arrest in the G1 and S phases at 55.82%. Finally, an in silico study was performed to explore the binding interaction of the most active compound within the zinc-containing binding site of HDAC6 and HDAC8.

Methoxychalcones as potential anticancer agents for colon cancer: Is membrane perturbing potency relevant?

Chalcones are naturally produced by many plants, and constitute precursors for the synthesis of flavons and flavanons. They were shown to possess antibacterial, antifungal, anti-cancer, and anti- inflammatory properties. The goal of the study was to assess the suitability of three synthetic methoxychalcones as potential anticancer agents. In a panel of colon cancer cell lines they were demonstrated to be cytotoxic, proapoptotic, causing cell cycle arrest, and increasing intracellular level of reactive oxygen species. Anticancer activity of the compounds was not diminished in the presence of stool extract containing microbial enzymes that could change the structure of chalcones. Moreover, methoxychalcones interacted strongly with model phosphatidylcholine membranes as detected by differential scanning calorimetry. Metohoxychalcones particularly affected the properties of lipid domains in giant unilamellar liposomes formed from raft-mimicking lipid composition. This may be of importance since many molecular targets for therapy of metastatic colon cancer are raft-associated receptors (e.g., receptor tyrosine kinases). The importance of membrane perturbing potency of methoxychalcones for their biological activity was additionally corroborated by the results obtained by molecular modelling.

Current scenario of chalcone hybrids with antibreast cancer therapeutic applications.

Breast cancer, an epithelial malignant tumor that occurs in the terminal ducts of the breast, is the most common female malignancy. Currently, approximately 70%-80% of breast cancer with early-stage, nonmetastatic disorder is curable, but the emergency of drug resistance often leads to treatment failure. Moreover, advanced breast cancer with distant organ metastases is incurable with the available therapeutics, creating an urgent demand to explore novel antibreast cancer agents. Chalcones, the precursors for flavonoids and isoflavonoids, exhibit promising activity against various breast cancer hallmarks, inclusive of proliferation, angiogenesis, invasion, metastasis, inflammation, stemness, and regulation of cancer epigenetics, representing useful scaffolds for the discovery of novel antibreast cancer chemotherapeutic candidates. In particular, chalcone hybrids could act on two or more different biological targets simultaneously with more efficacy, lower toxicity, and less susceptibility to resistance. Accordingly, there is a huge scope for application of chalcone hybrids to tackle the present difficulties in breast cancer therapy. This review outlines the chalcone hybrids with antibreast cancer potential developed from 2018. The structure-activity relationships as well as mechanisms of action are also discussed to shed light on the development of more effective and multitargeted chalcone candidates.

Development of multi-targetable chalcone derivatives bearing N-aryl piperazine moiety for the treatment of Alzheimer's disease.

The multi-target directed ligand (MTDL) discovery has been gaining immense attention in the development of therapeutics for Alzheimer's disease (AD). The strategy has been evolved as an auspicious approach suitable to combat the heterogeneity and the multifactorial nature of AD. Therefore, multi-targetable chalcone derivatives bearing N-aryl piperazine moiety were designed, synthesized, and evaluated for the treatment of AD. All the synthesized compounds were screened for thein vitro activityagainst acetylcholinesterase (AChE), butylcholinesterase (BuChE), ß-secretase-1 (BACE-1), and inhibition of amyloid ß (Aß) aggregation. Amongst all the tested derivatives, compound 41bearing unsubstituted benzylpiperazine fragment and para-bromo substitution at the chalcone scaffold exhibited balanced inhibitory profile against the selected targets. Compound 41 elicited favourable permeation across the blood-brain barrier in the PAMPA assay. The molecular docking and dynamics simulation studies revealed the binding mode analysis and protein-ligand stability ofthe compound with AChE and BACE-1. Furthermore,itameliorated cognitive dysfunctions and signified memory improvement in thein-vivobehavioural studies (scopolamine-induced amnesia model). Theex vivobiochemical analysis of mice brain homogenates established the reduced AChE and increased ACh levels. The antioxidant activity of compound 41 was accessed with the determination of catalase (CAT) and malondialdehyde (MDA) levels. The findings suggested thatcompound 41, containing a privileged chalcone scaffold, can act as a lead molecule for developing AD therapeutics.

Synthesis, biological evaluation and molecular modeling studies of modulated benzyloxychalcones as potential acetylcholinesterase inhibitors.

Acetylcholinesterase inhibitors (AChEIs) have become a significant target in the search for an efficient treatment of Alzheimer's disease. Chalcone-based compounds display a strong potency to hinder AChE. So, this study focused on the synthesis of a series of new chalcone derivatives with anti-cholinesterase potential and their structures were characterized based on spectroscopic methods including IR, 1H NMR, 13C NMR and HRMS. Chalcone derivatives were screened against AChE. Most of them exhibited potent inhibitory activity against AChE. Compound 11i showed the most potent activity toward acetylcholinesterase compared to the positive compound, Galantamine. Docking studies into the active site of the acetylcholinesterase enzyme ravealed the significant docking score of the synthesized compounds with docking score of -7.959 to -9.277 kcal/mol when compared to the co-crystallized ligand, Donepezil (-10.567 kcal/mol). The interaction's stability was further assessed using a conventional atomistic 100 ns dynamics simulation study, which revealed the conformational stability of representative compound 11i in the cavity of the acetylcholinesterase enzyme.Communicated by Ramaswamy H. Sarma.

Caesalpinflavans D-F and caesalpinnone B, hybrid flavan-chalcones and normonoterpene-chalcone heterodimer from Caesalpinia digyna.

Three undescribed hybrid flavan-chalcones, caesalpinflavans D-F, and an unreported normonoterpene-chalcone heterodimer, caesalpinnone B, along with three known biflavonoids were isolated from the twigs and leaves of Caesalpinia digyna. Their structures were elucidated based on extensive spectroscopic analysis and quantum chemical calculations. Caesalpinflavan F was identified as a bis-(hybrid flavan-chalcone), its natural occurrence was supported by HPLC-IT-TOF-MS analysis. The condensation of caesalpinflavan B with acetone was possibly a key step in the biosynthesis of caesalpinflavan F. Caesalpinnone B represents an unprecedented meroterpenoid featuring a cyclobutane central framework, which was derived from chalcone and normonoterpenoid via a key [2 + 2] cyclization reaction. Biological evaluation revealed that compounds caesalpinflavan D, oxytrodiflavanone A, and caesalpinnone B exhibited moderate cytotoxicity against HL-60, SMMC-7721, SW480, A-549 and/or MDA-MB-231 cell lines with IC50 values ranging from 8.051 ± 0.673 to 24.26 ± 0.61 µM. This study provided evidence for further research and possible utilization of C. digyna in the future.

Chalcone derivatives disrupt cell membrane integrity of Saccharomyces cerevisiae cells and alter their biochemical composition.

Fungal infections can be serious or life threatening in severe cases, and the need to discover and find novel antifungal agents persists. Chalcones are plant-derived aromatic compounds that have been appealing synthons for pharmaceutical industry as they have good anticancer, antibacterial, antifungal and anti-inflammatory properties. Although there are few structure-activity relationship studies on chalcones, studies that link the structural features of these compounds to their mode of action are scant. Thus, in this study, we aim to clarify the relationship between chalcone derivatives and their cellular target within the yeast cell Saccharomyces cerevisiae. We observed that some chalcone compounds lead to disruption of cell membrane and cause ion leakage out of the cell. Moreover, chalcones alter the biochemical composition of yeast cells detectable by FTIR spectroscopy and bind to the DNA as shown by our titration experiments based on UV-Vis absorbance spectroscopy. Thus, their interaction with the DNA may be the major impact of these compounds on yeast cells.

Novel 3-(pyrazol-4-yl)-2-(1H-indole-3-carbonyl)acrylonitrile derivatives induce intrinsic and extrinsic apoptotic death mediated P53 in HCT116 colon carcinoma.

A novel series of α-cyano indolylchalcones was prepared, and their chemical structures were confirmed based on the different spectral data. Among them, compound 7f was observed to be the most effective bioactive chalcone with distinguished potency and selectivity against colorectal carcinoma (HCT116) with IC50 value (6.76 µg/mL) relative to the positive control (5 FU) (77.15 µg/mL). In a preliminary action study, the acrylonitrile chalcone 7f was found to enhance apoptotic action via different mechanisms like inhibition of some anti-apoptotic protein expression, regulation of some apoptotic proteins, production of caspases, and cell cycle arrest. All mechanisms suggested that compound 7f could act as a professional chemotherapeutic agent. Also, a molecular docking study was achieved on some selected proteins implicated in cancer (Caspase 9, XIAP, P53 mutant Y220C, and MDM2) which showed variable interactions with compound 7f with good Gibbs free energy scores.

Natural Chalcones for the Management of Obesity Disease.

In the last decade, the incidence of obesity has increased dramatically worldwide, reaching a dangerous pandemic spread. This condition has serious public health implications as it significantly increases the risk of chronic diseases such as type 2 diabetes, fatty liver, hypertension, heart attack, and stroke. The treatment of obesity is therefore the greatest health challenge of our time. Conventional therapeutic treatment of obesity is based on the use of various synthetic molecules belonging to the class of appetite suppressants, lipase inhibitors, hormones, metabolic regulators, and inhibitors of intestinal peptide receptors. The long-term use of these molecules is generally limited by various side effects and tolerance. For this reason, the search for natural alternatives to treat obesity is a current research goal. This review therefore examined the anti-obesity potential of natural chalcones based on available evidence from in vitro and animal studies. In particular, the results of the main in vitro studies describing the principal molecular therapeutic targets and the mechanism of action of the different chalcones investigated were described. In addition, the results of the most relevant animal studies were reported. Undoubtedly, future clinical studies are urgently needed to confirm and validate the potential of natural chalcones in the clinical prophylaxis of obesity.

Network Pharmacology Combined with Machine Learning to Reveal the Action Mechanism of Licochalcone Intervention in Liver Cancer.

There are reports indicating that licochalcones can inhibit the proliferation, migration, and invasion of cancer cells by promoting the expression of autophagy-related proteins, inhibiting the expression of cell cycle proteins and angiogenic factors, and regulating autophagy and apoptosis. This study aims to reveal the potential mechanisms of licochalcone A (LCA), licochalcone B (LCB), licochalcone C (LCC), licochalcone D (LCD), licochalcone E (LCE), licochalcone F (LCF), and licochalcone G (LCG) inhibition in liver cancer through computer-aided screening strategies. By using machine learning clustering analysis to search for other structurally similar components in licorice, quantitative calculations were conducted to collect the structural commonalities of these components related to liver cancer and to identify key residues involved in the interactions between small molecules and key target proteins. Our research results show that the seven licochalcones molecules interfere with the cancer signaling pathway via the NF-κB signaling pathway, PDL1 expression and PD1 checkpoint pathway in cancer, and others. Glypallichalcone, Echinatin, and 3,4,3',4'-Tetrahydroxy-2-methoxychalcone in licorice also have similar structures to the seven licochalcones, which may indicate their similar effects. We also identified the key residues (including ASN364, GLY365, TRP366, and TYR485) involved in the interactions between ten flavonoids and the key target protein (nitric oxide synthase 2). In summary, we provide valuable insights into the molecular mechanisms of the anticancer effects of licorice flavonoids, providing new ideas for the design of small molecules for liver cancer drugs.

Discovery of a new dihydroeugenol-chalcone hybrid with cytotoxic and anti-migratory potential: A dual-action hit for cancer therapeutics.

Cancer still represents a serious public health problem and one of the main problems related to the worsening of this disease is the ability of some tumors to develop metastasis. In this work, we synthesized a new series of chalcones and isoxazoles derived from eugenol and analogues as molecular hybrids and these compounds were evaluated against different tumor cell lines. This structural pattern was designed considering the cytotoxic potential already known for eugenol, chalcones and isoxazoles. Notably, chalcones 7, 9, 10, and 11 displayed significant activity (4.2-14.5 µM) against two cancer cell lines, surpassing the potency of the control drug doxorubicin. The reaction of chalcones with hydroxylamine hydrochloride provided the corresponding isoxazoles that were inactive against these cancer cells. The dihydroeugenol chalcone 7 showed the most promising results, demonstrating higher potency against HepG2 (CC50: 4.2 µM) and TOV-21G (CC50: 7.2 µM). Chalcone 7 was also three times less toxic than doxorubicin considering HepG2 cells, with a selectivity index greater than 11. Further investigations including clonogenic survival, cell cycle progression and cell migration assays confirmed the compelling antitumoral potential of chalcone 7, as it reduced long-term survival due to DNA fragmentation, inducing cell death and inhibiting HepG2 cells migration. Moreover, in silico studies involving docking and molecular dynamics revealed a consistent binding mode of chalcone 7 with metalloproteinases, particularly MMP-9, shedding light on its potential mechanism of action related to anti-migratory effects. These significant findings suggest the inclusion of compound 7 as a promising candidate for future studies in the field of cancer therapeutics.

Conarubins A-D: Four Monoterpene-Chalcone Conjugates from Conamomum rubidum and Their Anti-inflammatory and Cytotoxic Activities.

Four novel compounds, conarubins A-D (1-4), were isolated from the whole plants of Conamomum rubidum collected in Vietnam. Their structures were elucidated by extensive spectroscopic analyses and by quantum chemical calculations of NMR and ECD. Compounds 1 and 2 were the first examples of monoterpene-monoterpene-chalcone conjugates in nature, whereas compound 4 was an unprecedented monoterpene-substituted chalcone containing a 3,4,5-trioxygenated cyclohexa-2,5-diene-1-one ring. The anti-inflammatory and cytotoxic activities of all isolates were investigated.

2-Acetyl-5,8-dihydro-6-(4-methyl-3-pentenyl)-1,4-naphthohydroquinone-Derived Chalcones as Potential Anticancer Agents.

Based on previous results with benzoindazolequinone (BIZQ) and 3-methylnaphtho [2,3-d]isoxazole-4,9-quinone (NIQ) derivatives, a novel series of chalcone-1,4-naphthoquinone/benzohydroquinone (CNQ and CBHQ) compounds were synthesized from 2-acetyl-5,8-dihydro-6-(4-methyl-3-pentenyl)-1,4-naphthohydroquinone. Their structures were elucidated via spectroscopy. These hybrids were assessed in vivo for their antiproliferative activity on MCF-7 breast adenocarcinoma and HT-29 colorectal carcinoma cells, revealing cytotoxicity with IC50 values between 6.0 and 110.5 µM. CBHQ hybrids 5e and 5f displayed enhanced cytotoxicity against both cell lines, whereas CNQ hybrids 6a-c and 6e exhibited higher cytotoxic activity against MCF-7 cells. Docking studies showed strong binding energies (ΔGbin) of CNQs to kinase proteins involved in carcinogenic pathways. Furthermore, our in silico analysis of drug absorption, distribution, metabolism, and excretion (ADME) properties suggests their potential as candidates for cancer pre-clinical assays.

Pharmacokinetic correlation of structurally modified chalcone derivatives as promising leads to treat tuberculosis.

In this study, we evaluated the potential of curated structurally modified chalcone derivatives as anti-tuberculosis (TB) agents through computer-aided drug design. Compounds from the flavonoid family known as chalcones were identified by the chemical group 1,3-diaryl-2-propen-1-one. After a search of the literature, 14 outstanding structurally modified chalcones were selected and evaluated for inhibitory activity against Mycobacterium tuberculosis H37Rv targets. The therapeutic potential of the chalcones was directly based on the drug-likeness and pharmacokinetic properties of the synthesized compounds. Prompt drug selection and personalized therapy are required to prevent TB from progressing and spreading to others. Pharmacokinetic parameters helps in the identification of lead molecule, at the earlier stages of drug development.