In silico docking and ADME study of deketene curcumin derivatives (DKC) as an aromatase inhibitor or antagonist to the estrogen-alpha positive receptor (Erα+): potent application of breast cancer

Abstract

Regardless of many extensive studies, hormonal-based breast cancer is the most common cause of cancer-related mortality of females worldwide. Indeed, estrogen receptor-positive (ER +) is the communal subtype in breast cancer. To treat this, three types of medications are typically used: selective estrogen receptor modulators (SERMs), selective estrogen receptor down modulators (SERDMs), and aromatase inhibitors (AIs), all of which directly interact with the activation of the estrogen signaling pathway and its formation. Despite their effectiveness, the development of new treatments is required since clinical efficacy is restricted owing to resistance. As a result, in silico studies for drug discovery are booming over the decades because of their affordability and less time-consuming features. Here, 25 deketene curcumin derivatives have been selected for docking studies through MVD software over the positive type of breast cancer through both the treatment hosts Erα + receptor and aromatase. DKC compounds are used because they have several pharmacological uses, including anti-cancer, anti-diabetic, anti-viral, anti-fungal, and anti-bacterial properties. Moreover, an ADME study was carried out for DKC derivatives that reveal the optimum drug-likeness profile. From 25 derivatives, the results showed a better MolDock score, hydrogen bonding, and steric interaction between compounds DKC-10, DKC-20, and DKC-21 with Erα + and aromatase. Although the study was done on both the treatable path hosts, better results were obtained with Erα + as an antagonist. Therefore, it is proposed that three selected DKC derivatives would be better therapeutic agents against breast cancer.

Integrated approach for studying bioactive compounds from Cladosporium spp. against estrogen receptor alpha as breast cancer drug target

“…Therefore, there is a lot of emphasis on developing new effective therapeutic drugs which specifically bind to estrogen receptor alpha and prevent the progression of hormone-dependent breast cancer. To date, many ligands such as estradiol, genistein, daidzein, biochanin A, 6,3’,4’-trihydroxyflavone, phloretin, ellagic acid, (-)-epigallocatechin-3-gallate, ursolic acid, kaempferol, naringenin, toxaphene, chlordane, thiadiazole acrylamide (XCT790), diethyl stilbestrol and deketene curcumin derivatives have been successfully identified as antagonists of estrogen receptor alpha by the virtual screening of structural model4 4 , 6 , 7 . Even though plants have long been utilized to treat several diseases, including cancer, the bioactive compounds produced by microbes have yet to be investigated.…”

Berberine modulates cardiovascular diseases as a multitarget-mediated alkaloid with insights into its downstream signals using in silico prospective screening approaches

“…TPSA is closely correlated with the H-bonding potentials of drugs and introduced as a good indicator for the drug bioavailability. Lead molecules with TPSA values ≥ 140 Å 2 represent poor intestinal absorption, and TPSA values < 90 Å 2 are needed to penetrate BBB and act on receptors in the CNS ( Srivastava, 2021 , Anandan et al, 2022 , Shah et al, 2022 ), which clearly presented as a good physicochemical characteristic of berberine. Recent studies reported that the drug oral bioavailability is positively correlated with the rotatable bond count ≤ 10 and TPSA ≤ 140 Å 2 ( Ayaz et al, 2020 , Anandan et al, 2022 ), which clearly observed and confirmed in this in silico study of berberine.…”

Inhibitory Potential of the Ocimum sanctum Phytochemicals on Bruton’s Tyrosine Kinase, a Well-Known Drug Target for Treatment of Chronic Lymphocytic Leukemia: An In Silico Investigation

“…The inhibitory potential of an inhibitor towards an enzyme or a protein receptor does not assure its suitability as an efficient drug [31]. The ADME analysis of the inhibitory compounds has been considered critical in drug discovery, as it helps in making the correct decision regarding the selection of inhibitors for evaluation in a living system [31][32][33]. Therefore, in the present study, the ADME analysis of the six top-ranked phytochemicals was performed for further screening, and selection of the best compounds possessing druglike characteristics (Table 2; Supplementary Table S1).…”

“…The analysis of the absorption, distribution, metabolism, and excretion (ADME) of the compounds has been reported very critical in drug discovery [31][32][33]. Therefore, the ADME study was conducted to analyse the drug-likeness, pharmacokinetics, and physicochemical properties of the selected phytochemicals using the web-based Swiss ADME tool (http://www.swissadme.ch (accessed on 2 March 2023)) [41].…”