Displaying publications 1 - 20 of 42 in total

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  1. Fu X, Sévenet T, Remy F, Païs M, Hamid A, Hadi A, et al.
    J Nat Prod, 1993 Jul;56(7):1153-63.
    PMID: 8377019
    Four complex flavanones, kurziflavolactones A [2], B [3], C [4], and D [5] and a complex chalcone 6 with an unprecedented carbon side chain on the flavanone or chalcone A ring have been isolated from a Malaysian plant, Cryptocarya kurzii (Lauraceae). Their structures were determined by extensive spectroscopic analysis, especially 2D nmr experiments. Compounds 3 and 6 showed slight cytotoxicity against KB cells, with IC50 values of 4 and 15 micrograms/ml, respectively. A biosynthetic pathway for the formation of these compounds is suggested.
    Matched MeSH terms: Chalcone/isolation & purification*; Chalcone/pharmacology; Chalcone/chemistry
  2. Sanjeeva Murthy TN, Naveen S, Chidan Kumar CS, Veeraiah MK, Quah CK, Siddaraju BP, et al.
    Acta Crystallogr E Crystallogr Commun, 2018 Aug 01;74(Pt 8):1134-1137.
    PMID: 30116578 DOI: 10.1107/S2056989018010216
    In the title chalcone-thio-phene derivative, C13H6Cl3FOS, the aromatic rings are inclined to one another by 12.9 (2)°, and the thio-phene ring is affected by π-conjugation. In the crystal, mol-ecules are linked by C-H⋯F hydrogen bonds, forming an R22(8) ring motif. A Hirshfeld surface analysis was conducted to verify the contribution of the different inter-molecular inter-actions. The shape-index surface clearly shows that the two sides of the mol-ecules are involved in the same contacts with neighbouring mol-ecules and the curvedness plots show flat surface patches characteristic of planar stacking.
    Matched MeSH terms: Chalcone; Chalcones
  3. Bukhari SN, Butt AM, Amjad MW, Ahmad W, Shah VH, Trivedi AR
    Pak J Biol Sci, 2013 Nov 01;16(21):1368-72.
    PMID: 24511749
    Hypertension is a widespread and frequently progressive ailment that imparts a foremost threat for cardiovascular and renal disorders. Mammoth efforts are needed for the synthesis of innovative antihypertensive agents to combat this lethal disease. Chalcones have shown antihypertensive activity through inhibition of Angiotensin Converting Enzyme (ACE). Hence, a series of chalcone analogues is synthesized and used as precursor for the synthesis of novel series of pyrimidines. Precursor chalcones were prepared by reacting aldehydes and ketones in presence of sodium hydroxide followed by synthesis of corresponding pyrimidines by reaction with urea in presence of potassium hydroxide. Both groups were then evaluated for their effects on ACE. The results depicted that pyrimidines were more active than chalcones with methoxy (C5 and P5) substitution showing best results to inhibit ACE. Given that chalcone analogues and pyrimidines show a potential as the angiotensin converting enzyme inhibitors.
    Matched MeSH terms: Chalcone/analogs & derivatives*; Chalcone/chemical synthesis; Chalcone/pharmacology*; Chalcone/chemistry
  4. Liew YJM, Lee YK, Khalid N, Rahman NA, Tan BC
    PeerJ, 2020;8:e9094.
    PMID: 32391211 DOI: 10.7717/peerj.9094
    Flavonoids and prenylated flavonoids are active components in medicinal plant extracts which exhibit beneficial effects on human health. Prenylated flavonoids consist of a flavonoid core with a prenyl group attached to it. This prenylation process is catalyzed by prenyltranferases (PTs). At present, only a few flavonoid-related PT genes have been identified. In this study, we aimed to investigate the roles of PT in flavonoid production. We isolated a putative PT gene (designated as BrPT2) from a medicinal ginger, Boesenbergia rotunda. The deduced protein sequence shared highest gene sequence homology (81%) with the predicted homogentisate phytyltransferase 2 chloroplastic isoform X1 from Musa acuminata subsp. Malaccensis. We then cloned the BrPT2 into pRI vector and expressed in B. rotunda cell suspension cultures via Agrobacterium-mediated transformation. The BrPT2-expressing cells were fed with substrate, pinostrobin chalcone, and their products were analyzed by liquid chromatography mass spectrometry. We found that the amount of flavonoids, namely alpinetin, pinostrobin, naringenin and pinocembrin, in BrPT2-expressing cells was higher than those obtained from the wild type cells. However, we were unable to detect any targeted prenylated flavonoids. Further in-vitro assay revealed that the reaction containing the BrPT2 protein produced the highest accumulation of pinostrobin from the substrate pinostrobin chalcone compared to the reaction without BrPT2 protein, suggesting that BrPT2 was able to accelerate the enzymatic reaction. The finding of this study implied that the isolated BrPT2 may not be involved in the prenylation of pinostrobin chalcone but resulted in high yield and production of other flavonoids, which is likely related to enzyme promiscuous activities.
    Matched MeSH terms: Chalcone; Chalcones
  5. Jantan I, Bukhari SN, Adekoya OA, Sylte I
    Drug Des Devel Ther, 2014;8:1405-18.
    PMID: 25258510 DOI: 10.2147/DDDT.S67370
    Arachidonic acid metabolism leads to the generation of key lipid mediators which play a fundamental role during inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as a synergistic anti-inflammatory effect with enhanced spectrum of activity. A series of 1,3-diphenyl-2-propen-1-one derivatives were investigated for anti-inflammatory related activities involving inhibition of secretory phospholipase A2, cyclooxygenases, soybean lipoxygenase, and lipopolysaccharides-induced secretion of interleukin-6 and tumor necrosis factor-alpha in mouse RAW264.7 macrophages. The results from the above mentioned assays exhibited that the synthesized compounds were effective inhibitors of pro-inflammatory enzymes and cytokines. The results also revealed that the chalcone derivatives with 4-methlyamino ethanol substitution seem to be significant for inhibition of enzymes and cytokines. Molecular docking experiments were carried out to elucidate the molecular aspects of the observed inhibitory activities of the investigated compounds. Present findings increase the possibility that these chalcone derivatives might serve as a beneficial starting point for the design and development of improved anti-inflammatory agents.
    Matched MeSH terms: Chalcone/analogs & derivatives*; Chalcone/chemical synthesis; Chalcone/pharmacology*; Chalcone/chemistry
  6. Kamaldin MN, Akhtar MN, Mohamad AS, Lajis N, Perimal EK, Akira A, et al.
    Molecules, 2013 Apr 10;18(4):4209-20.
    PMID: 23612473 DOI: 10.3390/molecules18044209
    Previous studies have shown that systemic administration of 6'-hydroxy-2',4'-dimethoxychalcone (flavokawin B, FKB) exerts significant peripheral and central antinociceptive effects in laboratory animals. However, the mechanisms underlying these peripheral and central antinociceptive effects have yet to be elucidated. Therefore, the objective of the present study was to evaluate the participation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/potassium (K+) channels pathway in the peripheral antinociception induced by FKB. It was demonstrated that intraplantar (i.pl.) administration of FKB (150, 250, 375 and 500 µg/paw) resulted in dose-dependent peripheral antinociception against mechanical hyperalgesia in carrageenan-induced hyperalgesia test model in rats. The possibility of FKB having either a central or a systemic effect was excluded since administration of FKB into the right paw did not elicit antinociception in the contralateral paw. Furthermore, peripheral antinociception induced by FKB (500 µg/paw) was significantly reduced when L-arginine (25 µg/paw, i.pl.), Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 µg/paw, i.pl.), glibenclamide (300 µg/paw, i.pl.), tetraethylammonium (300 µg/paw, i.pl.) and charybdotoxin (3 µg/paw, i.pl.) were injected before treatment. Taken together, our present data suggest that FKB elicits peripheral antinociception when assessed in the mechanical hyperalgesia induced by carrageenan. In addition, it was also demonstrated that this effect was mediated through interaction of the NO/cGMP/K+ channels signaling pathway.
    Matched MeSH terms: Chalcone/administration & dosage; Chalcone/pharmacology*
  7. Hassan NH, Abdullah AA, Arshad S, Khalib NC, Razak IA
    Acta Crystallogr E Crystallogr Commun, 2016 May 1;72(Pt 5):716-9.
    PMID: 27308026 DOI: 10.1107/S2056989016006526
    In the title chalcone derivative, C16H11ClF2O2, the enone group adopts an E conformation. The dihedral angle between the benzene rings is 0.47 (9)° and an intra-molecular C-H⋯F hydrogen bond closes an S(6) ring. In the crystal, mol-ecules are linked into a three-dimensional network by C-H⋯O hydrogen bonds and aromatic π-π stacking inter-actions are also observed [centroid-centroid separation = 3.5629 (18) Å]. The inter-molecular inter-actions in the crystal structure were qu-anti-fied and analysed using Hirshfeld surface analysis.
    Matched MeSH terms: Chalcone; Chalcones
  8. Bindya S, Chidan Kumar CS, Naveen S, Siddaraju BP, Quah CK, Raihan MA
    Acta Crystallogr E Crystallogr Commun, 2019 Feb 01;75(Pt 2):264-267.
    PMID: 30800464 DOI: 10.1107/S205698901900104X
    In the title chalcone derivative, C15H9BrCl2O, the aryl rings are inclined to each by 14.49 (17)°, and the configuration about the C=C bond is E. There is a short intra-molecular C-H⋯Cl contact present resulting in the formation of an S(6) ring motif. In the crystal, the shortest inter-molecular contacts are Cl⋯O contacts [3.173 (3) Å] that link the mol-ecules to form a 21 helix propagating along the b-axis direction. The helices stack up the short crystallographic a axis, and are linked by offset π-π inter-actions [inter-centroid distance = 3.983 (1) Å], forming layers lying parallel to the ab plane. A qu-anti-fication of the inter-molecular contacts in the crystal were estimated using Hirshfeld surface analysis and two-dimensional fingerprint plots.
    Matched MeSH terms: Chalcone; Chalcones
  9. Kiat TS, Pippen R, Yusof R, Ibrahim H, Khalid N, Rahman NA
    Bioorg Med Chem Lett, 2006 Jun 15;16(12):3337-40.
    PMID: 16621533
    Boesenbergia rotunda (L.) cyclohexenyl chalcone derivatives, 4-hydroxypanduratin A and panduratin A, showed good competitive inhibitory activities towards dengue 2 virus NS3 protease with the Ki values of 21 and 25 microM, respectively, whilst those of pinostrobin and cardamonin were observed to be non-competitive. NMR and GCMS spectroscopic data formed the basis of assignment of structures of the six compounds isolated.
    Matched MeSH terms: Chalcone/analogs & derivatives*; Chalcone/pharmacology*; Chalcone/chemistry*
  10. Maidur SR, Patil PS, Ekbote A, Chia TS, Quah CK
    Spectrochim Acta A Mol Biomol Spectrosc, 2017 Sep 05;184:342-354.
    PMID: 28528255 DOI: 10.1016/j.saa.2017.05.015
    In the present work, the title chalcone, (2E)-3-(4-fluorophenyl)-1-(4-{[(1E)-(4-fluorophenyl) methylene]amino}phenyl)prop-2-en-1-one (abbreviated as FAMFC), was synthesized and structurally characterized by single-crystal X-ray diffraction. The compound is crystallized in the monoclinic system with non-centrosymmetric space group P21 and hence it satisfies the essential condition for materials to exhibit second-order nonlinear optical properties. The molecular structure was further confirmed by using FT-IR and 1H NMR spectroscopic techniques. The title crystal is transparent in the Vis-NIR region and has a direct band gap. The third-order nonlinear optical properties were investigated in solution (0.01M) by Z-scan technique using a continuous wave (CW) DPSS laser at the wavelength of 532nm. The title chalcone exhibited significant two-photon absorption (β=35.8×10-5cmW-1), negative nonlinear refraction (n2=-0.18×10-8cm2W-1) and optical limiting (OL threshold=2.73kJcm-2) under the CW regime. In support of the experimental results, a comprehensive theoretical study was carried out on the molecule of FAMFC using density functional theory (DFT). The optimized geometries and frontier molecular orbitals were calculated by employing B3LYP/6-31+G level of theory. The optimized molecular structure was confirmed computationally by IR vibrational and 1H NMR spectral analysis. The experimental UV-Vis-NIR spectrum was interpreted using computational chemistry under time-dependent DFT. The static and dynamic NLO properties such as dipole moments (μ), polarizability (α), and first hyperpolarizabilities (β) were computed by using finite field method. The obtained dynamic first hyperpolarizability β(-2ω;ω,ω) at input frequency ω=0.04282a.u. is predicted to be 161 times higher than urea standard. The electronic excitation energies and HOMO-LUMO band gap for FAMFC were also evaluated by DFT. The experimental and theoretical results are in good agreement, and the NLO study suggests that FAMFC molecule can be a potential candidate in the nonlinear optical applications.
    Matched MeSH terms: Chalcone; Chalcones
  11. Suwito H, Jumina, Mustofa, Pudjiastuti P, Fanani MZ, Kimata-Ariga Y, et al.
    Molecules, 2014 Dec 19;19(12):21473-88.
    PMID: 25532844 DOI: 10.3390/molecules191221473
    Some chalcones have been designed and synthesized using Claisen-Schmidt reactions as inhibitors of the ferredoxin and ferredoxin-NADP+ reductase interaction to pursue a new selective antimalaria agent. The synthesized compounds exhibited inhibition interactions between PfFd-PfFNR in the range of 10.94%-50%. The three strongest inhibition activities were shown by (E)-1-(4-aminophenyl)-3-(4-methoxyphenyl)prop-2-en-1-one (50%), (E)-1-(4-aminophenyl)-3-(2,4-dimethoxyphenyl)prop-2-en-1-one (38.16%), and (E)-1-(4-aminophenyl)-3-(2,3-dimethoxyphenyl)prop-2-en-1-one (31.58%). From the docking experiments we established that the amino group of the methoxyamino chlacone derivatives plays an important role in the inhibition activity by electrostatic interaction through salt bridges and that it forms more stable and better affinity complexes with FNR than with Fd.
    Matched MeSH terms: Chalcone/analogs & derivatives*; Chalcone/chemical synthesis*
  12. de Toledo TA, da Costa RC, Al-Maqtari HM, Jamalis J, Pizani PS
    PMID: 28259100 DOI: 10.1016/j.saa.2017.02.051
    The heterocyclic chalcone containing thiophene ring 1-(4-chlorophenyl)-3-(2-thienyl)prop-2-en-1-one, C13H9ClOS was synthesized and investigated using experimental techniques such as nuclear magnetic resonance (1H and 13C NMR), Fourier transform infrared spectroscopy (FTIR) at room temperature, differential scanning calorimeter (DSC) from room temperature to 500K and Raman scattering at the temperature range 10-413K in order to study its structure and vibrational properties as well as stability and possible phase transition. Density functional theory (DFT) calculations were performed to determine the vibrational spectrum viewing to improve the knowledge of the material properties. A reasonable agreement was observed between theoretical and experimental Raman spectrum taken at 10K since anharmonic effects of the molecular motion is reduced at low temperatures, leading to a more comprehensive assignment of the vibrational modes. Increasing the temperature up to 393K, was observed the typical phonon anharmonicity behavior associated to changes in the Raman line intensities, line-widths and red-shift, in special in the external mode region, whereas the internal modes region remains almost unchanged due its strong chemical bonds. Furthermore, C13H9ClOS goes to melting phase transition in the temperature range 393-403K and then sublimates in the temperature range 403-413K. This is denounced by the disappearance of the external modes and the absence of internal modes in the Raman spectra, in accordance with DSC curve. The enthalpy (ΔH) obtained from the integration of the endothermic peak in DSC curve centered at 397K is founded to be 121.5J/g.
    Matched MeSH terms: Chalcone; Chalcones
  13. Sambasevam, Yogesvari, Wong, Siong Jiun, Farihah Hanani Ghazali, Ammar Izzati Amir Ramadan, Mohd Roslan Sulaiman, Mohd Khairi Hussain, et al.
    MyJurnal
    Introduction: Active compounds derived from plants are able to inhibit nerve conduction. Cardamonin, a naturally occurring chalcone, manifests anti-nociceptive, anti-inflammatory and anti-neuropathy properties. Consequently, cardamonin may potentially inhibit nerve action potential, whereby, it affects the nerve conduction. Compound action potential is the sum of the activity which is measured from a nerve trunk. Objective: The experiment was carried out to investigate the inhibitory effect of cardamonin on compound action potentials and its possible mechanism of action on frog sciatic nerve. Methodology: LabTutor software was used to record compound action potentials in frog sciatic nerve. Sciatic nerve was isolated from the frog and soaked in Ringer’s solution. Stimulating electrodes were used to stimulate the nerve and recording electrodes were used to record compound action potentials. Compound action potential of the nerve were recorded before and after treatments [vehicle, cardamonin (0.5, 1 & 2 mg/ml) & morphine (3mg/ml)]. Participation of opioid system was investigated by pre-treating the nerve with naloxone and followed by cardamonin. All the data were recorded and analysed via LabTutor software. The data were analysed by using Two-way ANOVA followed by Bonferonni’s post hoc test with significant value at P < 0.05. Results: The outcomes showed that all the doses of cardamonin significantly reduced the peak amplitude of compound action potential in frog sciatic nerves. Besides, co-treatment of naloxone and cardamonin significantly (P < 0.001) reversed the effect of cardamonin on peak amplitude of compound action potential, suggesting the involvement of opioid receptors to inhibit nerve conduction. Conclusion: Cardamonin reduces the nerve signal conduction via activation of opioid receptors to modulate pain and contribute to the analgesic effects.
    Matched MeSH terms: Chalcone; Chalcones
  14. Sambasevam Y, Omar Farouk AA, Tengku Mohamad TA, Sulaiman MR, Bharatham BH, Perimal EK
    Eur J Pharmacol, 2017 Feb 05;796:32-38.
    PMID: 27988285 DOI: 10.1016/j.ejphar.2016.12.020
    Neuropathic pain arises from the injury of nervous system. The condition is extremely difficult to be treated due to the ineffectiveness and presence of various adverse effects of the currently available drugs. In the present study, we investigated the antiallodynic and antihyperlagesic properties of cardamonin, a naturally occurring chalcone in chronic constriction injury (CCI)-induced neuropathic pain mice model. Our findings showed that single and repeated dose of intra-peritoneal administration of cardamonin (3, 10, 30mg/kg) significantly inhibited (P<0.001) the chronic constriction injury-induced neuropathic pain using the Hargreaves plantar test, Randall-Selitto analgesiometer test, dynamic plantar anesthesiometer test and the cold plate test in comparison with the positive control drug used (amitriptyline hydrochloride, 20mg/kg, i.p.). Pre-treatment with naloxone hydrochloride (1mg/kg, i.p.) and naloxone methiodide (1mg/kg, s.c) significantly reversed the antiallodynic and antihyperalgesic effects of cardamonin in dynamic plantar anesthesiometer test and Hargreaves plantar test, respectively. In conclusion, the current findings demonstrated novel antiallodynic and antihyperalgesic effects of cardamonin through the activation of the opioidergic system both peripherally and centrally and may prove to be a potent lead compound for the development of neuropathic pain drugs in the future.
    Matched MeSH terms: Chalcone; Chalcones
  15. Alias Y, Awang K, Hadi AH, Thoison O, Sévenet T, Païs M
    J Nat Prod, 1995 Aug;58(8):1160-6.
    PMID: 7595585
    Bioassay-guided fractionation of an ethyl acetate extract of Fissistigma lanuginosum led to the isolation of the known chalcone pedicin [1], which inhibited tubulin assembly into microtubules (IC50 value of 300 microM). From the same EtOAc fraction, two new condensed chalcones, fissistin [2] and isofissistin [3], which showed cytotoxicity against KB cells, were also obtained, together with the inactive dihydropedicin [4] and 6,7-dimethoxy-5,8-dihydroxyflavone [5]. In addition, the aminoquinones 6, 8, and 9 were isolated from the alkaloid extract. These compounds were artifacts, prepared by treatment of 1, 4, and 2, respectively, with NH4OH. The structures of the new compounds were elucidated by spectral methods, especially 2D nmr.
    Matched MeSH terms: Chalcone/analogs & derivatives*; Chalcone/isolation & purification; Chalcone/pharmacology
  16. Isa NM, Abdelwahab SI, Mohan S, Abdul AB, Sukari MA, Taha MM, et al.
    Braz. J. Med. Biol. Res., 2012 Jun;45(6):524-30.
    PMID: 22358425
    The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as the sample tested at 20 µg/mL. The toxic effect of BA on different cell types, reported as IC50, yielded 20.22 ± 3.15, 10.69 ± 2.64, 20.31 ± 1.34, 94.10 ± 1.19, and 9.324 ± 0.24 µg/mL for A549, PC3, HepG2, HT-29, and WRL-68, respectively. BA displayed considerable antioxidant activity, when the results of ORAC assay were reported as Trolox equivalents. BA (20 µg/mL) and quercetin (5 µg/mL) were equivalent to a Trolox concentration of 11.91 ± 0.23 and 160.32 ± 2.75 µM, respectively. Moreover, the anti-inflammatory activity of BA was significant at 12.5 to 50 µM and without any significant cytotoxicity for the murine macrophage cell line RAW 264.7 at 50 µM. The significant biological activities observed in this study indicated that BA may be one of the agents responsible for the reported biological activities of B. rotunda crude extract.
    Matched MeSH terms: Chalcone/isolation & purification; Chalcone/pharmacology*
  17. Abu Bakar NA, Sulaiman MR, Lajis N, Akhtar MN, Mohamad AS
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S711-S717.
    PMID: 33828366 DOI: 10.4103/jpbs.JPBS_344_19
    Introduction: Pain is a major global health issue, where its pharmacotherapy prompts unwanted side effects; hence, the development of effective alternative compounds from natural derivatives with lesser side effects is clinically needed. Chalcone; the precursors of flavonoid, and its derivatives have been widely investigated due to its pharmacological properties.

    Objective: This study addressed the therapeutic effect of 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative, on antinociceptive activity in vivo.

    Materials and Methods: The antinociceptive profile was evaluated using acetic-acid-induced abdominal writhing, hot plate, and formalin-induced paw licking test. Capsaicin, phorbol 12-myristate 12 acetate (PMA), and glutamate-induced paw licking test were carried out to evaluate their potential effects toward different targets.

    Results: It was shown that the doses of 0.1, 0.5, 1, and 5 mg/kg of DMPF-1 given via intraperitoneal injection showed significant reduction in writhing responses and increased the latency time in hot-plate test where reduced time spent on licking the injected paw in formalin and dose contingency inhibition was observed. The similar results were observed in capsaicin, PMA, and glutamate-induced paw licking test. In addition, the challenge with nonselective opioid receptor antagonist (naloxone) aimed to evaluate the involvement of the opioidergic system, which showed no reversion in analgesic profile in formalin and hot-plate test.

    Conclusion: Collectively, this study showed that DMPF-1 markedly inhibits both peripheral and central nociception through the mechanism involving an interaction with vanilloid and glutamatergic system regardless of the activation of the opioidergic system.

    Matched MeSH terms: Chalcone; Chalcones
  18. Moshawih S, Hadikhani P, Fatima A, Goh HP, Kifli N, Kotra V, et al.
    J Mol Graph Model, 2022 Dec;117:108307.
    PMID: 36096064 DOI: 10.1016/j.jmgm.2022.108307
    A Laplacian scoring algorithm for gene selection and the Gini coefficient to identify the genes whose expression varied least across a large set of samples were the state-of-the-art methods used here. These methods have not been trialed for their feasibility in cheminformatics. This was a maiden attempt to investigate a complete comparative analysis of an anthraquinone and chalcone derivatives-based virtual combinatorial library. This computational "proof-of-concept" study illustrated the combinatorial approach used to explain how the structure of the selected natural products (NPs) undergoes molecular diversity analysis. A virtual combinatorial library (1.6 M) based on 20 anthraquinones and 24 chalcones was enumerated. The resulting compounds were optimized to the near drug-likeness properties, and the physicochemical descriptors were calculated for all datasets including FDA, Non-FDA, and NPs from ZINC 15. UMAP and PCA were applied to compare and represent the chemical space coverage of each dataset. Subsequently, the Laplacian score and Gini coefficient were applied to delineate feature selection and selectivity among properties, respectively. Finally, we demonstrated the diversity between the datasets by employing Murcko's and the central scaffolds systems, calculating three fingerprint descriptors and analyzing their diversity by PCA and SOM. The optimized enumeration resulted in 1,610,268 compounds with NP-Likeness, and synthetic feasibility mean scores close to FDA, Non-FDA, and NPs datasets. The overlap between the chemical space of the 1.6 M database was more prominent than with the NPs dataset. A Laplacian score prioritized NP-likeness and hydrogen bond acceptor properties (1.0 and 0.923), respectively, while the Gini coefficient showed that all properties have selective effects on datasets (0.81-0.93). Scaffold and fingerprint diversity indicated that the descending order for the tested datasets was FDA, Non-FDA, NPs and 1.6 M. Virtual combinatorial libraries based on NPs can be considered as a source of the combinatorial compound with NP-likeness properties. Furthermore, measuring molecular diversity is supposed to be performed by different methods to allow for comparison and better judgment.
    Matched MeSH terms: Chalcone*; Chalcones*
  19. Lim YH, Oo CW, Koh RY, Voon GL, Yew MY, Yam MF, et al.
    Drug Dev Res, 2020 Jul 28.
    PMID: 32720715 DOI: 10.1002/ddr.21715
    In recent years, chalcones and their derivatives have become the focus of global scientists due to increasing evidence reported towards their potency in antitumor and anti-cancer. Here, the chalcones designed and synthesized in our present study were derived from the derivatives of naphthaldehyde and acetophenone. Both these precursors have been reported in demonstrating a certain degree of anticancer property. Also, the substituents on these precursors such as hydroxyl, methoxy, prenyl, and chloro were shown able to enhance the anticancer efficiency. Hence, it is the interest of the current study to investigate the anticancer potential of the hybrid molecules (chalcones) consisting of these precursors with different alkoxy substituents and with or without the fluorine moiety. Two series of chalcone derivatives were designed, synthesized, and characterized using the elemental analysis, IR, 1 H and 13 C NMR spectroscopy, subsequently evaluated for their anti-cancer activity. Interestingly, the results showed that the fluorinated chalcones 11-15 exhibited stronger cytotoxic activity towards the breast cancer cell lines (4T1) compared to non-fluorinated chalcone derivatives. Remarkably, the selectivity index obtained for these fluorinated chalcones derivatives against the breast cancer 4T1 cell line was higher than those exhibited by cisplatin, which is one of the most frequently deployed chemotherapy agents in current medical practice. These findings could provide an insight towards the potential of fluorinated chalcones being developed as an anti-cancer agent with moderate activity towards breast cancer cell and low inhibition of fibroblast cell at a concentration of 100 μM.
    Matched MeSH terms: Chalcone; Chalcones
  20. Konidala SK, Kotra V, Danduga RCSR, Kola PK
    Bioorg Chem, 2020 11;104:104207.
    PMID: 32947135 DOI: 10.1016/j.bioorg.2020.104207
    Four series of thirteen new coumarin-chalcone hybrids (DPCU 1-13, DPCT 1-13, DCCU 1-13 and DCCT 1-13) were designed and synthesized using Biginelli synthesis, Pechmann condensation, Acetylation, and Claisen-Schmidt reactions. Synthesized compounds were tested for insulin receptor in silico docking studies (PDB ID: 1IR3); DCCU 13 and DCCT 13 derivatives received the lowest docking score; Streptozocin (STZ) and Nicotinamide (NA) induced type II diabetes was tested for their anti-diabetic activity in rats. In vivo tests suggested that fasting blood glucose levels of animals treated with DCCU 13 (30 mg/kg body weight) and DCCT 13 (30 mg/kg body weight) were significantly and moderately suppressed, respectively, relative to fasting blood glucose levels of diabetic control animals. Similarly, therapy with DCCU 13 and DCCT 13 attenuated oxidative stress parameters such as lipid peroxidation (MDA), superoxide dismutase (SOD) and increased the glutathione (GSH) in the liver and pancreas in a dose-dependent manner. In comparison, therapy with DCCU 13 (30 mg/kg body weight) mitigated alterations in the histological architecture of the liver and pancreatic tissue. These results indicated that the hybrids DUUC 13 and DCCT 13 at 30 mg/kg had an anti-hyperglycemic and antioxidant impact on STZ + NA mediated type II diabetes in rats. Further detailed work could be required to determine the precise mode of action of the anti-diabetic behavior of hybrids.
    Matched MeSH terms: Chalcone/administration & dosage; Chalcone/pharmacology*; Chalcone/chemistry
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