1840-01-3Relevant articles and documents
Flavone-based hydrazones as new tyrosinase inhibitors: Synthetic imines with emerging biological potential, SAR, molecular docking and drug-likeness studies
Alsantali, Reem?I.,Mughal, Ehsan?Ullah,Naeem, Nafeesa,Alsharif, Meshari?A.,Sadiq, Amina,Ali, Anser,Jassas, Rabab.?S.,Javed, Qamar,Javid, Asif,Sumrra, Sajjad Hussain,Alsimaree, Abdulrahman?A.,Zafar, Muhammad?Naveed,Asghar, Basim?H.,Altass, Hatem?M.,Moussa, Ziad,Ahmed, Saleh?A.
, (2021/11/30)
Targeting tyrosinase (TYR), a key enzyme responsible for melanogenesis disorders, is a well-known approach utilized for the development of melanogenesis inhibitor. A variety of dermatological disorders and microbial skin infections can cause hyperpigmentation. Hence, exploring new scaffolds for the treatment of melanogenesis disease is an inspiring goal. In this context, a series of varyingly substituted flavone-based hydrazones have been designed, synthesized and characterized successfully. The present study describes the discovery of novel mushroom tyrosinase inhibitors (TIs) for treating hyperpigmentation. In due course, flavone scaffold has been incorporated into the novel chemotypes that exhibit in vitro inhibitory effects against mushroom tyrosinase for the purpose of discovering anti‐melanogenic agents. Biological investigations of prepared analogs herein demonstrated moderate to excellent activity against most of the fungal-bacterial strains and their activity is comparable to those of commercially available antibiotics i.e., Ciprofloxacin and Ketoconazole. Based on in vitro tyrosinase inhibitory assay, some compounds exhibited potent inhibition particularly, 3g (IC50 = 1.40 ± 0.16 μM), 3j (IC50 = 0.95 ± 0.07 μM), 3o (IC50 = 1.13 ± 0.11 μM), and 3q (IC50 = 1.01 ± 0.1 μM) showed best inhibition i.e., 0.7, 0.5, 0.6 and 0.5 folds, respectively, than kojic acid (IC50 = 1.79 ± 0.6 μM). Lineweaver-Burk plots demonstrated that the most potential derivative 3j tyrosinase inhibition proceeds via non-competitive pathway and the Michaelis-Menton constant (Km) value is 0.0265. Molecular modeling was performed for all tested analogs (3a–3q) using a model of mushroom tyrosinase to find crucial binding modes liable for inhibitory activity. The SARs were preliminarily examined, and the docking study revealed that analogs 3j, 3o and 3p had a strong binding association to tyrosinase (2Y9X). Furthermore, a drug-likeness study was employed and confirmed the favorable activity of the new analogs as a new anti-tyrosinase agent.
Stereoselective reduction of flavanones by marine-derived fungi
Birolli, Willian G.,Nitschke, Marcia,Porto, André Luiz M.,Santos, Darlisson de A.,de Matos, Iara L.
, (2021/08/13)
Biotransformation is an alternative with great potential to modify the structures of natural and synthetic flavonoids. Therefore, the bioreduction of synthetic halogenated flavanones employing marine-derived fungi was described, aiming the synthesis of flavan-4-ols 3a-g with high enantiomeric excesses (ee) of both cis- and trans-diastereoisomers (up to >99% ee). Ten strains were screened for reduction of flavanone 2a in liquid medium and in phosphate buffer solution. The most selective strains Cladosporium sp. CBMAI 1237 and Acremonium sp. CBMAI1676 were employed for reduction of flavanones 2a-g. The fungus Cladosporium sp. CBMAI 1237 presented yields of 72–87% with 0–64% ee cis and 0–30% ee trans with diastereoisomeric ratio (dr) from 52:48 to 64:36 (cis:trans). Whereas Acremonium sp. CBMAI 1676 resulted in 31% yield with 77–99% ee of the cis and 95–99% ee of the trans-diastereoisomers 3a-g with a dr from 54:46 to 96:4 (cis:trans). To our knowledge, this is the first report of the brominated flavon-4-ols 3e and 3f. The use of fungi, with emphasis for these marine-derived strains, is an interesting approach for enantioselective reduction of halogenated flavanones. Therefore, this strategy can be explored to obtain enantioenriched compounds with biological activities.
Experimental and theoretical insights into the photophysical and electrochemical properties of flavone-based hydrazones
Ahmed, Ishtiaq,Ahmed, Safeer,Ahmed, Saleh A.,Alsantali, Reem I.,Alsharif, Meshari A.,Altaf, Ataf Ali,Altass, Hatem M.,Jassas, Rabab. S.,Kausar, Samia,Mughal, Ehsan Ullah,Mumtaz, Amara,Naeem, Nafeesa,Obaid, Rami J.,Sadiq, Amina,Zafar, Muhammad Naveed
, (2021/07/06)
A small library of flavone-based hydrazones has been designed, synthesized and characterized. In this context, thirteen flavone hydrazones (3a-3 m) were synthesized by the acid-catalyzed condensation of flavone with 2,4-dinitrophenylhydrazine (2,4-DNPH) and characterized by different spectral techniques (IR, UV–Vis, NMR and mass spectrometry). The electrochemical, photophysical and theoretical investigations of such type of compounds are hitherto unknown. The electrochemical behavior of these hydrazones at a platinum electrode has been analyzed by cyclic voltammetry (CV) and was investigated at 200, 100 and 40 mVs?1 in acetonitrile (CH3CN). These hydrazones showed a quasi-reversible redox reaction. The oxidation–reduction reactive sites of these derivatives were located via geometry optimization using density functional theory (DFT) at the B3LYP/3–21 g in the Guassian-09 level of theory. Moreover, the target compounds exhibited interesting fluorescent properties. Owing to their excellent photophysical and redox results, a detailed structure-property relationship was established to assess the substituents impact and their position on the physicochemical and electronic properties. All the experimental results were in accordance with the computational studies.
