Naphthyl Research Articles

Synthesis, structures, DFT studies and properties of novel tertiary diphosphines based on α- and β-naphthylamine

Based on α- and β-naphthylamine, two new diphosphines, N,N-bis((diphenylphos phino)methyl)naphthalen-1-amine (1) and N,N-bis((diphenylphosphino)methyl)naphthalene -2-amine (2), have been prepared and characterized by IR, 1H NMR, 31P NMR, TG, UV-Vis, XRD and X-ray crystal structure analysis. Structural analysis shows that the two Ph2PCH2- groups in 1 and 2 are disposed in an anti configuration, and the change of the position of the (Ph2PCH2)2N-group on the naphthalene moiety results in different spatial configurations of the two Ph2P- groups and different weak interactions, such as C-H…π and π–π interactions. DFT studies show that the composition of the HOMOs for 1 and 2 are almost the same (the naphthyl group with admixed N and P atoms), but the ingredients of the LUMOs for 1 are different from that for 2, coinciding with the change of Mülliken atomic charges. Moreover, the emission spectra show that the emissions of complexes 1 and 2 in acetonitrile solution are not similar to those of solid-state samples.

Synthesis, Characterization, and Cytotoxicity of Morpholine-Containing Ruthenium(II) p-Cymene Complexes.

Morpholine motif is an important pharmacophore and, depending on the molecular design, may localize in cellular acidic vesicles. To understand the importance of the presence of pendant morpholine in a metal complex, six bidentate N,O-donor ligands with or without a pendant morpholine unit and their corresponding ruthenium(II) p-cymene complexes (1-6) are synthesized, purified, and structurally characterized by various analytical methods including X-ray diffraction. Complexes 2-4 crystallized in the P21/c space group, whereas 5 and 6 crystallized in the P1̅ space group. The solution stability studies using 1H NMR support instantaneous hydrolysis of the native complexes to form monoaquated species in a solution of 3:7 (v/v) dimethyl sulfoxide-d6 and 20 mM phosphate buffer (pH* 7.4, containing 4 mM NaCl). The monoaquated complexes are stable for at least up to 24 h. The complexes display excellent in vitro antiproliferative activity (IC50 ca. 1-14 μM) in various cancer cell lines, viz., MDA-MB-231, MiaPaCa2, and Hep-G2. The presence of the pendant morpholine does not improve the dose efficacy, but rather, with 2-[[(2,6-dimethylphenyl)imino]methyl]phenol (HL1) and its pendant morpholine analogue (HL3) giving complexes 1 and 3, respectively, the antiproliferative activity was poorer with 3. MDA-MB-231 cells treated with the complexes show that the acidic vesicles remain acidic, but the population of acidic vesicles increases or decreases with time of exposure, as observed from the dispersed red puncta, depending on the complex used. The presence of the 2,6-disubstituted aniline and the naphthyl group seems to improve the antiproliferative dose. The complex treated MDA-MB-231 cells show that cathepsin D, which is otherwise present in the cytosolic lysosomes, translocates to the nucleus as a result of exposure to the complexes. Irrespective of the presence of a morpholine motif, the complexes do not activate caspase-3 to induce apoptosis and seem to favor the necrotic pathway of cell killing.

Synthesis, Spectroscopic, and 1O2 Sensitization Characteristics of Extended Pd(II) 10,10-Dimethylbiladiene Complexes Bearing Alkynyl-Aryl Appendages.

Photodynamic therapy (PDT), which involves the photoinduced sensitization of singlet oxygen, is an attractive treatment for certain types of cancer. The development of new photochemotherapeutic agents remains an important area of research. Macrocyclic tetrapyrrole compounds including porphyrins, phthalocyanines, chlorins, and bacteriochlorins have been pursued as sensitizers of singlet oxygen for PDT applications but historically are difficult to prepare/purify and can also suffer from high nonspecific dark toxicity, poor solubility in biological media, and/or slow clearance from biological tissues. In response to these shortcomings, we have developed a series of novel linear tetrapyrrole architectures complexed to late transition metals as potential PDT agents. We find that these dimethylbiladiene (DMBil1) tetrapyrrole complexes can efficiently photosensitize generation of 1O2 oxygen upon irradiation with visible light. To extend the absorption profile of the DMBil1 platform, alkynyl-aryl groups have been conjugated to the periphery of the tetrapyrrole using Sonogashira methods. Derivatives of this type containing ancillary phenyl (DMBil-PE), naphthyl (DMBil-NE), and anthracenyl (DMBil-AE) groups have been prepared and characterized. In addition to structurally characterizing Pd[DMBil-NE] and Pd[DMBil-AE], we find that extension of the tetrapyrrole conjugation successfully red-shifts the absorption of the DMBil-Ar family of biladienes further into the phototherapeutic window (i.e., 600-900 nm). Photochemical sensitization studies demonstrate that our series of new palladium biladiene complexes (Pd[DMBil-Ar]) can sensitize the formation of 1O2 with quantum yields in the range ΦΔ = 0.59-0.73 upon irradiation with light of λ ≥ 650 nm. The improved absorption properties of the Pd[DMBil-Ar] complexes in the phototherapeutic window, together with their high 1O2 quantum yields, highlight the promise of these compounds as potential agents for PDT.

Design, Synthesis and Characterization of Molecular Components for Light Induced Molecular Machines

Molecular machines are systems of molecules that convert chemical energy into mechanical forces. They have a range of potential applications such as transportation of chemicals or use as an arity signal for computation. In literature, most molecular machines are activated through some form of chemical signal. This has a range of drawbacks from limiting the range of environments the machine can function in to the buildup of byproducts of the chemical reaction. The solution to these limitations was found in the synthesis and characterization of various light induced molecular machines. Like the name implies, this subset of molecular machines uses light as the signal that activates the mechanism. The model of molecular machine being worked on in this research is a porphyrin-based molecular shuttle shown in scheme 1.Upon photoexcitation of the porphyrin acceptor, represented by the symbol A, an electron transfer from naphthyl group to the porphyrin occurs. Following this photoinduced electron transfer, a radical pair is formed between the porphyrin and naphthyl group. The newly generated naphthyl cation is expected to drive the macrocycle situated around the naphthalene towards the aryl group due to the more favourable interactions. Upon relaxation of the radical pair through back electron transfer, the macrocycle is expected to return to the naphthalene group due to the regeneration of the electron density on the naphthyl group. In this context, novel molecular machine components have been synthesized and characterized using various spectroscopic and electrochemical techniques. The goal of which, is to fine tune the chemical, physical and synthetical properties such that they are suitable for future use in a complete molecular machine as described in scheme 1. Figure 1

DNA-Intercalative Platinum Anticancer Complexes Photoactivated by Visible Light.

Photoactivatable agents offer the prospect of highly selective cancer therapy with low side effects and novel mechanisms of action that can combat current drug resistance. 1,8‐Naphthalimides with their extended π system can behave as light‐harvesting groups, fluorescent probes and DNA intercalators. We conjugated N‐(carboxymethyl)‐1,8‐naphthalimide (gly‐R‐Nap) with an R substituent on the naphthyl group to photoactive diazido PtIV complexes to form t,t,t‐[Pt(py)2(N3)2(OH)(gly‐R‐Nap)], R=H (1), 3‐NO2 (2) or 4‐NMe2 (3). They show enhanced photo‐oxidation, cellular accumulation and promising photo‐cytotoxicity in human A2780 ovarian, A549 lung and PC3 prostate cancer cells with visible light activation, and low dark cytotoxicity. Complexes 1 and 2 exhibit pre‐intercalation into DNA, resulting in enhanced photo‐induced DNA crosslinking. Complex 3 has a red‐shifted absorption band at 450 nm, allowing photoactivation and photo‐cytotoxicity with green light.

Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy

Hormone therapy targeting estrogen receptors is widely used clinically for the treatment of breast cancer, such as tamoxifen, but most of them are partial agonists, which can cause serious side effects after long-term use. The use of selective estrogen receptor down-regulators (SERDs) may be an effective alternative to breast cancer therapy by directly degrading ERα protein to shut down ERα signaling. However, the solely clinically used SERD fulvestrant, is low orally bioavailable and requires intravenous injection, which severely limits its clinical application. On the other hand, double- or multi-target conjugates, which are able to synergize antitumor activity by different pathways, thus may enhance therapeutic effect in comparison with single targeted therapy. In this study, we designed and synthesized a series of novel dual-functional conjugates targeting both ERα degradation and histone deacetylase inhibiton by combining a privileged SERD skeleton 7-oxabicyclo[2.2.1]heptane sulfonamide (OBHSA) with a histone deacetylase inhibitor side chain. We found that substituents on both the sulfonamide nitrogen and phenyl group of OBHSA unit had significant effect on biological activities. Among them, conjugate 16i with N-methyl and naphthyl groups exhibited potent antiproliferative activity against MCF-7 cells, and excellent ERα degradation activity and HDACs inhibitory ability. A further molecular docking study indicated the interaction patterns of these conjugates with ERα, which may provide guidance to design novel SERDs or PROTAC-like SERDs for breast cancer therapy.

Mesomorphic Behavior of Symmetric Azomethine Dimers Containing Different Chromophore Groups.

A series of new azomethine dimers was synthesized by the condensation reaction of flexible bis-benzaldehydes with four aromatic amines containing phenyl, naphthyl, anthracene and pyrene groups. Their right structure was confirmed by FTIR and 1H-NMR spectroscopy and their thermal properties were investigated by thermogravimetric analysis, differential scanning calorimetry and polarized light optical microscopy. A view on their photophysical behavior was gained by UV-vis and photoluminescence spectroscopy. The dimers containing pyrene and anthracene presented liquid crystalline behavior, while the other dimers were crystalline compounds. Two dimers containing pyrene moieties formed mesomorphic glasses and had intense luminescence, promising properties for applications in building optoelectronic devices.

Electric and steric hindrance effects of substituents on luminescence and force-stimuli response of cyanovinyl phenothiazine derivatives

Six cyanovinyl phenothiazine derivatives bearing substituents with different sizes, and electron-donating and -withdrawing abilities were designed and synthesized. The effect of substituents on photophysical properties in solution and solid states were systematically investigated. The results suggested that electron-donating groups almost did not influence absorption and emission properties in solutions because the distributions of molecular HOMOs and LUMOs were independent of electron-donating groups. In contrast, trifluoromethyl (CF3) and cyano as electron-withdrawing units induced bathochromic shifts in both absorption and fluorescence spectra owing to the decrease in LUMO energy levels. Furthermore, it was found that the photophysical properties in crystal states strongly depended on the terminal substituent. Larger tert-butyl (t-butyl), methoxy and CF3 groups resulted in smaller spectral shifts in relative to smaller groups after crystallization. Single crystal structures suggested both CF3 and CN units lead a poor π-stacking, but charge transfer existed in PCVCN crystals. J-type dimers were found in PCVH and PCVN crystals. More interestingly, t-butyl, CF3 and methoxy moieties induced obvious color conversion and larger spectral shifts of 76 nm, 66 nm and 55 nm, respectively, under force stimuli. On the other hand, the compounds with terminal hydrogen atom, naphthyl and cyano group possessed shifts of 46 nm, 34 nm and 23 nm.

Structure-based Discovery of Cell-Potent Peptidomimetic Inhibitors for Protein N-Terminal Methyltransferase 1.

Protein N-terminal methyltransferases (NTMTs) catalyze the methylation of the α-N-terminal amines of proteins starting with an X-P-K/R motif. NTMT1 has been implicated in various cancers and in aging, implying its role as a potential therapeutic target. Through structural modifications of a lead NTMT1 inhibitor, BM30, we designed and synthesized a diverse set of inhibitors to probe the NTMT1 active site. The incorporation of a naphthyl group at the N-terminal region and an ortho-aminobenzoic amide at the C-terminal region of BM30 generates the top cell-potent inhibitor DC541, demonstrating increased activity on both purified NTMT1 (IC50 of 0.34 ± 0.02 μM) and the cellular α-N-terminal methylation level of regulator of chromosome condensation 1 (RCC1, IC50 value of 30 μM) in human colorectal cancer HT29 cells. Furthermore, DC541 exhibits over 300-fold selectivity to several methyltransferases. This study points out the direction for the development of more cell-potent inhibitors for NTMT1.

Ni-catalyzed enantioselective [2 + 2 + 2] cycloaddition of malononitriles with alkynes

Summary Efficient strategies to assemble enantioenriched pyridine derivatives are highly important, given their significance in both synthetic and medicinal chemistry. Here, we report an enantioselective nickel-catalyzed intermolecular [2 + 2 + 2] cycloaddition of alkyne-tethered malononitriles with alkynes for the synthesis of densely substituted pyridines. The α-all-carbon quaternary center adjacent to pyridine is introduced by desymmetrizing the two cyano groups of disubstituted malononitriles. Notably, terminal alkynes are also tolerated with good regioselectivity to afford tetrasubstituted pyridines. Zinc halide is essential to enable the occurrence of the transformation by promoting the hetero-cyclometallation step. The reaction uses bio-renewable 2-MeTHF as the solvent and features mild reaction conditions, good functional group compatibilities, and enantioselectivities. This study offers a straightforward approach to the valuable enantioenriched heteroarenes from feedstock chemicals by forming three bonds and one quaternary stereocenter simultaneously in a single reaction step.

Synthesis, spectral, stereochemical, biological, molecular docking and DFT studies of 3-alkyl/3,5-dialkyl-2r,6c-di(naphthyl)piperidin-4-one picrates derivatives

A new series of 3-alkyl/3,5-dialkyl-2r,6c-di(naphthyl)piperidin-4-one picrates (1-6) were synthesized their chemical structures were confirmed by elemental analysis, FT-IR, 1H and 13C NMR and mass spectral techniques and for compound 4 was characterized by HOMOCOSY, HSQC, HMBC, NOESY, and DEPT NMR spectral techniques. From the NMR spectral data, the observed chemical shifts and coupling constants suggested that compounds (1-6) adopt a normal chair conformation with equatorial orientation of all the naphthyl groups at C-2 and C-6 and alkyl group at C-3 and C-5 and from the 1H chemical shifts H-5a and H-3a have a higher magnitude than H-5e. This is due to 1,3 diaxial interaction between axial NH proton and axial protons at C-3 and C-5. The synthesized compounds were screened for their bacterial activity against Escherichia coli, Staphylococcus aureus, Bacillus.subtilis, Vibreo cholerae and Pseudomonas aeruginosa and fungal activity against Candida albicans, Aspergillus niger, Aspergillus flavus and Trichophyton rubrum. All the compounds showed good antibacterial and antifungal activities. The optimized molecular structure of the synthesized compounds (1-6) were studied by using DFT/B3LYP/6-311++G(d,p) basis set. The calculated electrical dipole moment (µ) and first hyperpolarizability (βo) values shows that all the molecules might have nonlinear optical (NLO) behavior. The HOMO-LUMO transition implies that intra-molecular charge transfer takes place within the molecule. Molecular electrostatic potential (MEP) surface is used to understand the reactive sites of a molecule. To establish information about the molecular interactions between protein and this novel compound theoretically, docking studies were carried out in detail.

Fluorescence and phosphorescence of α- and β-isomers of boron Difluoride naphthaloylacetonates

A comparative study of the luminescence properties of solutions and crystals of two isomers: boron difluoride 1-(1′-naphthyl)butanedionate-1,3 (α-NAcBF2) and 1-(2′-naphthyl)butanedionate-1,3 (β-NAcBF2) has been performed. An interrelation between the molecular and crystal structure of the studied complexes and their luminescence properties has been revealed. In the α-NAcBF2 molecule, the plane of the naphthyl group was turned by 34.26° relatively to the chelate cycle, while the β-NAcBF2 molecule was planar. The difference in the luminescence properties of the crystals of α-NAcBF2 (452 nm) and β-NAcBF2 (537 nm) was related to different abilities to form excimers. In β-NAcBF2 crystals, J-aggregates consisted of dimers of antiparallel molecules comprising excimer traps. For the crystals and solutions of α-NAcBF2 at 77 K, in addition to phosphorescence, the delayed fluorescence was observed. In case of β-NAcBF2, the delayed fluorescence was detected only for crystals, whereas the phosphorescence – for both crystals and solutions.

Synthesis, X-ray, Hirshfeld surface analysis, exploration of DNA binding, urease enzyme inhibition and anticancer activities of novel adamantane-naphthyl thiourea conjugate

1-(adamantane-1-carbonyl-3-(1-naphthyl)) thiourea (C22H24N2OS (4), was synthesized by the reaction of freshly prepared adamantane-1-carbonyl chloride from corresponding acid (3) with ammonium thiocyanate in 1:1 M ratio in dry acetone to afford the adamantane-1-carbonyl isothiocyanate (2) in situ followed by treatment with 1-naphthyl amine (3). The structure was established by elemental analyses, FTIR, 1H, 13C NMR and mass spectroscopy. The molecular and crystal structure were determined by single crystal X-ray analysis. It belongs to triclinic system P − 1 space group with a = 6.7832(5) Å, b = 11.1810(8) Å, c = 13.6660(10) Å, α = 105.941(6)°, β = 103.730(6)°, γ = 104.562(6)°, Z = 2, V = 910.82(11) Å3. The naphthyl group is almost planar. In the crystal structure, intermolecular CH···O hydrogen bonds link the molecules into centrosymmetric dimers, enclosing R22(14) ring motifs, while the intramolecular NH···O hydrogen bonds enclose S(6) ring motifs, in which they may be effective in the stabilization of the structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H … H (59.3%), H … C/C … H (19.8%) and H … S/S … H (10.1%) interactions. Hydrogen bonding and van der Waals interactions are the dominant interactions in the crystal packing. DFT, molecular docking and urease inhibition studies revealed stability and electron withdrawing nature of 4 as compared to DNA base pairs and residues of urease. The DNA binding results from docking, UV– visible spectroscopy, and viscosity studies indicated significant binding of 4 with the DNA via intercalation and groove binding. Further investigation of the compound was done on hepatocellular carcinoma; Huh-7 cell line as well as normal human embryonic kidney; Hek-293 cell line. The compound showed significant cytotoxic activity against Huh-7 cells in comparison to normal Hek-293 cells indicating selective cytotoxicity towards cancer cells.

Enantiopure Calcium Iminophosphonamide Complexes: Synthesis, Photoluminescence, and Catalysis

The synthesis of calcium complexes ligated by three different chiral iminophosphonamide ligands, L‐H (L=[Ph2P{N(R)CH(CH3)Ph}2]), L′‐H (L′=[Ph2P{NDipp}{N(R)CH(CH3)Ph}]), (Dipp=2,6‐iPr2C6H3), and L′′‐H (L′′=[Ph2P{N(R)CH(CH3)naph}2]), (naph=naphthyl) is presented. The resulting structures [L 2Ca], [L′ 2Ca], and [L′′ 2Ca] represent the first examples of enantiopure homoleptic calcium complexes based on this type of ligands. The calcium complexes show blue–green photoluminescence (PL) in the solid state, which is especially bright at low temperatures. Whereas the emission of [L′′ 2Ca] is assigned to the fluorescence of naphthyl groups, the PL of [L 2Ca] and [L′ 2Ca] is contributed by long‐lived phosphorescence and thermally activated delayed fluorescence (TADF), with a strong variation of the PL lifetimes over the temperature range of 5–295 K. Furthermore, an excellent catalytic activity was found for these complexes in hydroboration of ketones at room temperature, although no enantioselectivity was achieved.

Novel asymmetrical bis-surfactants with naphthalene and two amide groups: Synthesis, foamability and foam stability

A series of novel asymmetrical bis-surfactants (CnNCS, n = 10, 12, 14, 16), comprising a naphthalene group and a long chain hydrocarbon (as hydrophobic moieties), a quaternary ammonium group, one ether group and double amides (as hydrophilic moieties), and ethylidene as linkage groups, were designed, prepared, and characterized through proton and carbon nuclear magnetic resonance, Fourier-transform infrared, and electrospray ionization mass spectrometry analyses. The surface activity was studied by surface tension measurements. CnNCS exhibited low critical micelle concentrations (0.708–0.004 mmol L−1) and excellent surface tension reducing abilities. Moreover, the introduction of naphthyl and amido groups into C12NCS significantly enhanced the foamability and foam stability. This is attributed mainly to cooperative noncovalent interactions such as hydrophobic interactions of the long chain hydrocarbons, π-π stacking of the naphthyl groups, hydrogen-bonding of the amido groups of C12NCS itself and hydrogen bonding of C12NCS with water, and electrostatic interaction, which induced a decrease in the surface tension, leading to a compact and dense arrangement of the C12NCS molecules at the air–water interface to form a tight film. Both features enabled foam formation, slowed liquid drainage from the foam, and prevented the gas from diffusing through the monolayer, thus enhancing the foam stability. In addition, the long-acting emulsifying ability of C12NCS and good antibacterial activity of CnNCS were also demonstrated. Moreover, hydrogen-bonding of the amido groups and π-π stacking of the naphthyl groups of CnNCS were verified from the 1H NMR and fluorescence spectra, respectively. This work provides a feasible strategy for the synthesis of highly efficient foaming, emulsifying, and bacteriostatic agents.

A sterically shielded design on anthracene-based emitters for efficient deep-blue organic light-emitting diodes

Two new anthracene derivatives are designed with a sterically shielded strategy for deep-blue electroluminescence applications. The naphthyl groups of the widely used blue emitter 9,10-di-(2-naphthyl)anthracene (ADN) were modified with four peripheral phenyl groups (PPGs) to enhance intermolecular spacing in solid-state thin film for suppressing electronic coupling. Influence of the PPGs decoration on photoluminescence and electroluminescence are investigated to reveal the structure-property relationship. A nondoped organic light-emitting diode with the new emitter 9-(naphthalen-2-yl)-10-(5,6,7,8-tetraphenylnaphthalen-2-yl)anthracene (M1) exhibits excellent performance with a maximum external quantum efficiency of 5.05% and deep-blue color index of (0.15, 0.09). Although the use of bulky peripheral substituents does improve device performance, it should be paid attention to the non-conductive effect induced by the larger molecular spacing in the design of deep-blue electroluminescence materials. This work provides a promising molecular design for deep-blue electroluminescence materials.

Marked effects of azulenyl vs. naphthyl groups on donor-π-acceptor-π-donor small molecules for organic photovoltaic cells

Although the unique electronic and optical properties of azulene, the azulene-containing organic photovoltaic (OPV) materials have sporadically reported. Here, eight donor-π-acceptor-π-donor conjugated OPV materials entailing guaiazulene or naphthalene as electron donor unit were synthesized and characterized. The azulenyl and naphthyl groups have significant influences on their molecular properties and photovoltaic performances. Compared to naphthalene derivatives, azulene derivatives exhibit red-shifted and wider absorption spectra. However, naphthalene derivatives exhibit much deeper highest occupied molecular orbital (HOMO) energy levels, higher hole mobility and better film morphology, remarkably resulting in approximately 2–4 times higher photovoltaic efficiencies than azulene derivatives.

A fluorescent calix[4]arene with naphthalene units at the upper rim exhibits long fluorescence emission lifetime without fluorescence quenching.

We synthesised a new compound with four naphthyl groups in the upper rims of calix[4]arene (1). Compared to the monomer unit, compound 1 has redshifted absorption and fluorescence, together with high fluorescence quantum yield and long fluorescence lifetime, which is extremely rare because long fluorescence lifetime emission tends to reduce the quantum yield. Single-crystal X-ray analysis and quantum calculations in the S1 state revealed π–π through-space interactions between naphthalene rings.

Ethylene oligomerisation chromium catalysts with unsymmetrical PCNP ligands.

Chromium(iii) complexes of chelating diphosphines, with PNP or PCNCP backbones, are excellent catalysts for ethylene tetra- and/or trimerisations. A missing link within this ligand series are unsymmetric chelating diphosphines based on a PCNP scaffold. New bidentate PCNP ligands of the type Ph2PCH2N(R)PPh2 (R = 1-naphthyl or 5-quinoline groups, 2a-d) have been synthesised and shown to be extremely effective ligands for ethylene tri-/tetramerisations. Three representative tetracarbonyl Cr0 complexes bearing a single PN(R)P (5), PCN(R)P (6), or PCN(R)CP (7) diphosphine (R = 1-naphthyl) have been prepared from Cr(CO)4(η4-nbd) (nbd = norbornadiene). Furthermore we report a single crystal X-ray diffraction study of these compounds and discuss their structural parameters.

Identification of novel C-2 symmetric Bis-Azo-Azamethine molecules as competitive inhibitors of mushroom tyrosinase and free radical scavengers: synthesis, kinetics, and molecular docking studies

Tyrosinase is a multi-copper enzyme found in plants, animals and microorganisms, plays a critical role in the melanogenesis and browning process critical to cosmetics and food industries. Many natural, semi-synthetic and synthetic inhibitors have been discovered. To this end, a small library of symmetrical Bis-Azo-Azamethine hybrids 5a–j was synthesized and characterized through spectroscopic and analytical data and explored for mushroom tyrosinase and free radical scavenging activity. All of the molecules 5a–j explicated better potential compared to the standard Kojic acid. On the whole, compound 5i having IC50 value 0.002 ± 0.004 µM was found to be the most potent derivative. The Kinetic studies were performed for 5i and indicating the mode of inhibition in a competitive manner. Structure Activity Relationship (SAR) analysis and docking studies were carried out. Thus compound 5i bearing bulky naphthyl groups was most potent and, The molecular docking indicated formation of two hydrogen bonds with Arg268 and one hydrophobic interaction with Glu322. The carbonyl oxygen of 5i interacts with Arg268 and form two hydrogen bonds having lengths 2.44 and 2.62 Å, respectively. In the same way, compounds 5a–j were appraised for DPPH free radical scavenging ability and five of them 5d, 5e, 5h, 5i and 5j were found to exhibit higher % scavenging potency compared with vitamin C, as the standard. Interesting compound 5i was again the most potent in the series. The current investigation points towards the role of naphthyl group in design of new inhibitors of melanogenesis and the antioxidants with improved efficacy. Communicated by Ramaswamy H. Sarma