Spectroscopic X-ray Research Articles

Isolation and Biomimetic Semisynthesis of Hyperzrones A and B, Two Nor-Polycyclic Polyprenylated Acylphloroglucinols with a Characteristic Cyclobutane Moiety, from Hypericum beanii.

Hyperzrones A (1) and B (2), two unprecedented nor-polycyclic polyprenylated acylphloroglucinols with a characteristic cyclobutane moiety, were discovered from Hypericum beanii. Their structures were determined by extensive spectroscopic analysis, X-ray crystallography, and quantum chemical calculation methods. A bioinspired semisynthesis of 1 and 2 was achieved from the natural precursor hypercalin B (3), featuring a Favorskii-type rearrangement and a visible-light-mediated [2 + 2] photocycloaddition. Several diverse derivatives were also obtained, providing a compound library for biological studies.

The In Vitro Cytotoxic Potential of Biosynthesized Silver Nanoparticles in MIA PaCa-2 Cells Supported with an In Silico Study

Pancreatic cancer affects many people and is quite aggressive. Metallic nanoparticles may be an alternative treatment for this disease. In this work, the antiproliferative activity of biosynthesized silver nanoparticles was evaluated. Stenocereus queretaroensis peel extract was used as a reducing agent for nanoparticle synthesis; the characterization was carried out using spectroscopic techniques, X-ray diffraction, and microscopy. The antiproliferative effect was evaluated in the MIA PaCa-2 pancreatic tumoral cell line, and a molecular docking test was run with the STAT3 protein. The results obtained show that it was possible to synthesize silver nanoparticles from the plant extract, which was confirmed through characterization studies. The average size of the nanoparticles was measured to be 48.8 nm, and they predominantly exhibited a spherical shape. The antiproliferative effect was demonstrated in the pancreatic cell line, with an IC50 value of 15.66 µg/mL. The molecular docking analysis predicted a strong interaction with the STAT3 protein, with a binding energy value of −6.47 obtained. With these results, it is concluded that biosynthesized silver nanoparticles inhibit pancreatic tumor cell growth and may represent an innovative cancer treatment.

Clean and Efficient Green Protocol of N,N'-Bis(2-(arylazo)-2-(aroyl)vinyl)ethane-1,2-diamines in Aqueous Medium without Catalyst: Synthesis and Photophysical Characterization.

An interesting platform for the construction of novel N,N'-bis(2-(arylazo)-2-(aroyl)vinyl)ethane-1,2-diamines is reported in this work. These bis-arylazo compounds were assembled based on the reaction of ethylenediamine with various 2-arylhydrazono-3-oxopropanals in aqueous conditions under both conventional stirring and microwave conditions at ambient temperature. The factors affecting the optimization conditions were intensively practiced. The structures of the new products were established from their spectroscopic analyses and X-ray single crystals. The photophysical behavior of the bis-arylazo derivatives was examined. The UV-vis spectra showed maximum absorption band in the range of 348-383 nm with molar extinction coefficients ranging from 0.89 × 104 to 4.02 × 104 M-1 cm-1. The highest molar absorptivity coefficient (∼45 × 103 M-1 cm-1) was observed in CHCl3 solvent. The fluorescence properties showed that some compounds were interesting fluorophore materials with high Stokes shifts. The photoluminescence study of some compounds was promising, with maximal emission peaks ranging between 417-436 nm.

Elucidating the ruthenium-mediated conversion of aryl alkynes to alkoxy(benzyl)carbene and benzyl carbonyl complexes

Metal vinylidenes are key intermediates in the activation of terminal alkynes. Previous studies concerning ruthenium η6-arene complexes showed how the elusive vinylidenes are often transformed into more stable alkoxy(alkyl)carbene complexes upon reaction with alcohols, highlighting their electrophilicity. We reinvestigated the reactivity of terminal alkynes and alcohols with ruthenium(II) η6-arene precursors and we found out new aspects of the formation and the reactivity of the alkoxy(carbene)complexes. First, the reactivity of ruthenium complexes bearing different η6-arene, phosphane, halide co-ligands on the activation process of a series of arylalkynes have been examined. Under optimized conditions, a series of alkoxy(benzyl)carbene complexes of general formula [RuCl{C(OR’)CH2(4-C5H4R)}(PR’’3)(η6-arene)]+ were obtained. Five compounds were isolated in 82–96 % yield and they were characterized by spectroscopic techniques and X-ray diffraction in three cases. Notably, these carbene complexes are the predominant reaction products even in presence of a large molar excess of water in the mixture for short reaction times.In fact, DFT calculations on a model system showed that the vinylidene intermediate, resulting from the Ru/alkyne interaction, is preferentially attacked by MeOH instead of water. The subsequent formation of carbonyl complexes was assessed in various conditions by IR and NMR and four unprecedented and comparatively rare benzyl carbonyl complexes of general formula [Ru{CH2(4-C6H4R)}(CO)(PPh3)(η6-arene)]+ are reported, including the crystal structure of one example. Next, an unprecedented reactivity study on selected alkoxy(benzyl)carbene complexes was carried out. Joint experimental and computational results indicate that these benzyl carbonyl complexes may actually arise from the reaction of the carbene complexes with water, a reactivity pathway that has never been considered in previous studies on the Ru-mediated hydrolytic cleavage of alkynes.

Synthesis, crystal structure, cytotoxicity (MCF-7 and HeLa) and free radical scavenging activity of the hydrazones derived from 2-methylsulfonyl-5-nitrobenzaldehyde

The rising levels of breast and cervical cancers among women have become public health problem with high economic burden globally and more especially in low- and middle-income countries. This necessitates discoving new and potent anticancer drugs with reduced or no side effects. The hydrazones derived from 2-formyl-4-nitrophenyl methanesulfonate were characterized using a combination of spectroscopic and single-crystal X-ray diffraction (XRD) techniques. The compounds were, in turn, evaluated for antigrowth effect in vitro against the human breast adenocarcinoma (MCF-7) and human cervical cancer (HeLa) cell lines and for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The presence of a chlorine atom on the para position of the phenylhydrazone moiety of 3b resulted in increased cytotoxicity against the MCF-7 and the HeLa cell lines compared to camptothecin (IC50 = 9.15 ± 0.84 µM and 3.71 ± 0.16 µM, respectively) with IC50 values of 5.64 ± 0.84 µM and 2.40 ± 0.13 µM, respectively. Compounds 2, 3a and 3b were found to exhibit significantly reduced toxicity against the Vero cells compared to the anti-cancer drugs, doxorubicin (IC50 = 0.78 ± 0.04 µM) and nintedanib (IC50 = 0.24 ± 0.02 µM) with the IC50 values of 17.86 ± 1.12, 11.89 ± 1.01 and 24.42 ± 0.70 µM, respectively. The hydrazones 3a and 3b exhibited a strong inhibitory effect against the vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase (IC50 = 5.78 ± 0.039 μM and 5.79 ± 0.053 µM, respectively) compared to the carbaldehyde precursor 2 (IC50 = 8.01 ± 0.052 µM) though less active compared to nintedanib (IC50 = 1.05 ± 0.193 µM). The hydrazone derivatives exhibited significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity compared to ascorbic acid and the parent 2-formyl-4-nitrophenylmethanesulfonate. In silico molecular docking studies revealed the binding potential of the hydrazones at the active site of VEGFR-2 tyrosine kinase and cytochrome c peroxidase.

Synthesis of 1,3-oxazines based on piperazine

The oxazines bearing piperazinyl moieties namely 2-(tert-butyl)-6-((4-(2-(8-(tert-butyl)-6-methyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)ethyl)piperazin-1-yl)methyl)-4-methylphenol (1) and its corresponding 2,4-di-tert-butyl-6-((4-(2-(6,8-di-tert-butyl-2H-benzo[e]-[1,3]oxazin-3(4H)-yl)ethyl)piperazin-1-yl)methyl)phenol (2), which was previously isolated were described. The transformation of the piperazinyl tri-tert-butyl-phenol derivatives 6,6′-(((2-(4-(3-(tert-butyl)-2-hydroxy-5-methylbenzyl)piperazin-1-yl)ethyl)-azanediyl)bis-(methylene))bis-(2-(tert-butyl)-4-methylphenol) 3 and 6,6′-(((2-(4-(3,5-di-tert-butyl-2-hydroxybenzyl)piperazin-1-yl)ethyl)-azanediyl)-bis(methylene))bis(2,4-di-tert-butyl-phenol) 4 into 1 and 2, respectively was achieved in high yield by heating and stirring a methanolic solution containing Et3N and Ga(NO3)3·6H2O in the stochiometric ratio 1:3:1 for 30 min. The novel oxazine-piperazine 1 together with its triphenol-piperazine 3 (H3L4) were structurally characterized by spectroscopic and single crystal X-ray crystallography.

Role of the Coreactant on the Dual-Source Behavior of Lithium Hexamethyldisilazide for ALD Li-Containing Films.

Atomic layer deposition (ALD) of Li-containing thin films is deemed as highly relevant for the development of next-generation Li-ion batteries. Lithium hexamethyldisilazide (LiHMDS), as Li-containing precursor, is preferred over the widely used lithium tert-butoxide because of its lower melting point of 70 °C. However, the presence of silyl groups in the LiHMDS chemical structure can result in the undesired incorporation of Si in the film. Therefore, understanding the reaction mechanism of LiHMDS is required to control its dual-source behavior and grow Si-free Li-containing thin films. For this purpose LiHMDS was combined with O2 plasma or water as coreactant. In situ spectroscopic ellipsometry (SE) and X-ray photoelectron spectroscopy (XPS) revealed that using O2 plasma as coreactant results in linear growth and Si-containing films, whereas using H2O as coreactant leads to fast, nonsurface-reaction-limited growth and Si-free films. To shed light on the role of the coreactant on the reaction mechanism of LiHMDS, in situ studies by time-resolved quadrupole mass spectrometry (QMS) were performed on the O2 plasma and H2O-based ALD processes. Measurements taken during full ALD cycles and half-cycles were carefully compared to identify which half-cycle surface reaction products lead to silicon incorporation in the film. The QMS results of the LiHMDS + H2O process showed that LiHMDS both chemisorbs and physisorbs. Furthermore, it is concluded that Si incorporation occurs during the O2 plasma step, when the physisorbed ligands are combusted and Si-containing products are redeposited. This work also demonstrates that the incorporated Si can be abstracted from the film by means of a H2 plasma step following the O2 plasma step. These insights on the role of the coreactant in the synthesis of Li-containing films contribute to the development of LiHMDS-based ALD processes for Li-ion battery applications.

Beautoide A, an Anti-Osteoclastogenic Sterol from Beauveria sp. NBUF147 Associated with an Irciniidae Sponge from the Marine Mesophotic Zone.

Mesophotic coral ecosystems (MCEs), located at depths ranging from 30-150 m, host some of the most diverse yet least explored marine bioresources, particularly significant for the discovery of new bioactive molecules. The fungus Beauveria sp. NBUF147, associated with an Irciniidae sponge from the mesophotic zone at a depth of 82 m, underwent chemical investigation that led to the identification of one new sterol, beautoide A (1), and one reported sterol, 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (2). Their structures were determined from analysis of spectroscopic data and X-ray crystallography. Evaluation of biological activity in prednisolone-induced osteoporotic zebrafish showed that 1 was anti-osteoclastogenic in vivo at 3.0 μM.

Structurally diverse triterpenoids with antibacterial activities from Euphorbia humifusa

An exploration of antibacterial components from the whole plant of Euphorbia humifusa led to the isolation of 14 new triterpenoids, euphohumifusoids A–N (1–7 and 9–15), as well as four known analogues (8 and 16–18). Their structures were elucidated by extensively analysis of the spectroscopic data and X-ray crystallography using Cu Kα radiation. Among them, euphohumifusoid A (1) bears an unique 6(7 → 8)abeo scaffold originated from a D:C-friedo-oleanane skeleton for the first time, euphohumifusoids H and I (9 and 10) possess a rare α,β-unsaturated-γ-lactone chain originated from 25,26,27-trinordammaranes, and euphohumifusoid L (13) is a highly modified 3,4-seco-25,26,27-trinorcycloartane. Notably, in antibacterial bioassay, compound 1 displayed excellent antibacterial activities against Bacillus cereus, Staphylococcus aureus, and S.epidermidis with MIC of 12.5, 25, and 25 μg/mL, comparable to the positive controls. Upon exposure to 1 and 2 MIC of 1, B.cereus underwent drastic morphological changes, resulting in complete disruption of the cells. Meanwhile, compound 1 also exhibited remarkable antibiofilm activity against B.cereus at 1 MIC and 2 MIC.

Gigantolevisins A–C, tyrosinase inhibitory benzylidenes from the shoots of Gigantochloa levis

The excessive tyrosinase activity has been linked to the overproduction of melanin which can lead to hyperpigmentation, oxidative stress, browning, and an increased risk of melanoma. Due to these detrimental effects associated with the overexpression of tyrosinase, research efforts are focused on finding bioactive compounds that can inhibit this enzyme efficiently. This study, conducted to find tyrosinase inhibitors utilizing the shoots of Gigantochloa levis (G. levis), produced three previously undescribed benzylidene derivatives (1–3) and two known compounds, with promising anti-tyrosinase activity. The new compounds were designated as gigantolevisins A–C, and the two known compounds as (E)-3-(4-hydroxyphenyl)-2-phenylacrylaldehyde (4) and (E)-2,3-bis(4-hydroxyphenyl)acrylaldehyde (5), respectively, based on the spectroscopic data and X-ray crystallographic analysis. The isolated compounds showed inhibition effects against tyrosinase, ranging from 42 % to 58 % (IC50 values of >400–286 ± 15 μM) in comparison to the positive control Kojic acid with 100 % inhibition (IC50 value of 43 ± 3 μM). The findings suggest that, while the isolated compounds are less potent than Kojic acid, they can be effective in inhibiting tyrosinase activity. Thus, the study highlights the therapeutic potential of G. levis shoots for treating melanin-related conditions.

Infiltration of glass nanofiber-reinforced polylactic acid into delignified hardwood toward photoluminescent and mechanically reliable smart windows

Ultraviolet-protective, mechanically reliable, and photoresponsive wood that can switch color under ultraviolet light was developed. A combination of alkaline earth-doped strontium aluminate (ASA) as a photoluminescent pigment and glass nanofiber-supported polylactic acid as a hosting agent was infused into a delignified wood, producing transparent wood with photochromic activity. The ASA phosphor has proven high thermal stability and photostability. A typical process for producing colorless photoluminescent wood includes the well-dispersion of ASA in glass nanofiber-supported polylactic acid without agglomeration. As proven by the coloration measurements, the current photoluminescent wood becomes green under ultraviolet light and remains transparent under daylight. Transmission electron microscopy (TEM) and scanning electron microscope (SEM) were employed to determine the morphology of the phosphor particles and glass fibers, demonstrating sizes of 12–21 nm and 50–125 nm, respectively. The luminescent wooden samples were studied by numerous microscopic and spectroscopic techniques, including SEM, X-ray fluorescence (XRF), and energy-dispersive X-ray (EDX). Upon excitation at 365 nm, the luminescence wood demonstrated an emission peak at 518 nm. When increasing the ASA concentration, the photoluminescent hardwoods displayed improved ultraviolet protection and better water resistance. The responsiveness of the luminescent wood to UV irradiation was fast and reversible.

Two isoledene-type sesquiterpenoids from a soft coral Heteroxenia sp.

Two new isoledene-type sesquiterpenoids, 1 and 2, were isolated from an Okinawan soft coral Heteroxenia sp. The planar structures and stereochemistry of 1 and 2 were determined by spectroscopic analysis, X-ray crystallography, and comparison of experimental and calculated ECD studies. Antiviral and anti-leishmania assays were performed. Compound 2 exhibited activity against promastigotes of Leishmania major.

New oligomeric terpenoids fused with an oxazoline ring linkage from cones of Taxodium ascendens and their biological activities

Taxodascaloids A-C (1–3), three uncommon oligomeric terpenoids featuring an oxazoline ring linkage, were purified from the cones of Taxodium ascendens. Compounds 1 and 2, a unique pair of stereoisomers, represented the first identified diterpenoid-monoterpenoid adducts linked by an oxazoline ring. Compound 3 was an uncommon dimeric diterpenoid and composed of a seco-abietane unit and an abietane unit, also containing an oxazoline ring. The planar structures and absolute configurations of these compounds were determined using extensive spectroscopic analysis and X-ray diffraction techniques. Compounds 1 and 2 demonstrated potent anticancer activity against human colon cancer HCT cells, with the IC50 values of 25.7 and 40.1 μM, respectively. Further research indicated that compound 1 could induce both ferroptosis and apoptosis in HCT-116 cells. Additionally, compound 3 showed notable α-glucosidase inhibitory activity in a mixed-type manner with an IC50 value of 2.9 μM.

Synthesis and BSA binding study of the Cu(II) complex and applications of it to enhance catalytic activity for C(Sp2)-H bond functionalization and for the synthesis of polyhydroquinolines

Among the various copper-catalyzed coupling reactions, C–S and C–N bond-forming reactions have carried off plentiful recognition due to their demand in the synthesis of molecules having biological and pharmaceutical impact. Organo-copper complex has an incontestable supremacy over the other catalytic complex due to its low cost and the use of readily accessible and stable ligands. As a consequence and in continuation of our explorative studies in this direction, an efficient and novel organo-copper complex has been synthesized and characterized by spectroscopic (NMR, FT-IR) and single crystal X-ray diffraction (XRD) methods. The synthesized stable metal complex has fascinating physical, chemical, biological and catalytic properties. In the chemical exploration refer to protein-metal interactions; we have often used Bovine Serum Albumin (BSA) protein. The synthesized copper complex has the potential to form coordinate bonds with functional groups present in BSA, together with amino acid residues and the protein backbone. The binding of metal complexes to BSA has outstanding imputation in medicinal chemistry. For enhancement of the catalytic activity of the organo-copper complex, we have evaluated it in carbon-hetero bond formation reactions where it proffered an influential tool for the establishment of C–S and C–N bonds.

Structural and spectroscopic characterization of the peridinin-chlorophyll a-protein (PCP) complex from Heterocapsa pygmaea (HPPCP)

Light harvesting proteins are optimized to efficiently collect and transfer light energy for photosynthesis. In eukaryotic dinoflagellates these complexes utilize chlorophylls and a special carotenoid, peridinin, and arrange them for efficient excitation energy transfer. At the same time, the carotenoids protect the system by quenching harmful chlorophyll triplet states. Here we use advanced spectroscopic techniques and X-ray structure analysis to investigate excitation energy transfer processes in the major soluble antenna, the peridinin chlorophyll a protein (PCP) from the free living dinoflagellate Heterocapsa pygmaea. We determined the 3D-structure of this complex at high resolution (1.2 Å). For better comparison, we improved the reference structure of this protein from Amphidinium carterae to a resolution of 1.15 Å. We then used fs and ns time-resolved absorption spectroscopy to study the mechanisms of light harvesting, but also of the photoprotective quenching of the chlorophyll triplet state. The photoprotection site was further characterized by Electron Spin Echo Envelope Modulation (ESEEM) spectroscopy to yield information on water molecules involved in triplet-triplet energy transfer.Similar to other PCP complexes, excitation energy transfer from peridinin to chlorophyll is found to be very efficient, with transfer times in the range of 1.6–2.1 ps. One of the four carotenoids, the peridinin 614, is well positioned to quench the chlorophyll triplet state with high efficiency and transfer times in the range of tens of picoseconds. Our structural and dynamic data further support, that the intrinsic water molecule coordinating the chlorophyll Mg ion plays an essential role in photoprotection.

Exploring the synthesis, characterization, crystal structures, DFT calculation, hirshfeld surface analysis, and anticancer activity of Ni(II) complex of 1-(4-nitrobenzoyl)-4-phenyl-3-thiosemicarbazide

The chemistry of biologically active thiosemicarbazide has been of interest to researchers owing to its diverse application and bonding features. In the present study, a new thiosemicarbazide derivative namely 1-(4-nitrobenzoyl)-4-phenyl-3-thiosemicarbazide (HnbphTSC) has been prepared and along with its [Ni(nbphTSC)2(en)]·CHCl3 (1) complex. The prepared ligand (HnbphTSC) and complex 1 have been characterized through spectroscopic and single-crystal X-ray data. The HnbphTSC and complex 1 crystallize in triclinic and monoclinic crystal systems with space groups P1¯ and P21/C, respectively. The weak interactions present in HnbphTSC and complex 1 have been quantitively studied through hirshfeld surface analysis. The physiochemical characteristics of HnbphTSC and complex 1 are also verified using DFT calculations, and the resultant results are in strong agreement with the experimental findings. The HOMO and LUMO energy gap have been calculated as 3.160 eV and 2.212 eV for HnbphTSC and complex 1, respectively. MTT assay was used to evaluate the cytotoxicity of HnbphTSC and complex 1 against Dalton's lymphoma (DL) cells. We further assessed the mode of tumor cell death and the drug's effect on nuclear condensation and plasma membrane integrity by employing DAPI/PI dual staining technique.

Synthesis and Structure Revision of Securingine E.

Chemical synthesis plays a crucial role in confirming and revising the structures of natural products. Through meticulous synthetic efforts, NMR spectroscopic and single-crystal X-ray diffraction analyses, DFT calculations, and mass spectrometric investigations, we revised the structure of securingine E. The revised structure of securingine E was unambiguously confirmed by its chemical synthesis.

Crafting copper complexes of variable nuclearity and coordination geometry through solvent tailoring: Unveiling novel structure, magnetic insight and computational marvels

The solvent tuning technique has been employed to synthesize two new copper complexes [Cu3(L)(NO3)2(DMSO)4] (1) and [Cu6(L)2(NO3)2(DMF)4(H2O)2(µ-HCOO)2] (2) which display variable nuclearity and coordination geometries. The synthesized complexes further characterized by using spectroscopic, single crystal and powder X-ray diffraction techniques. Supramolecular assembly of the complexes in the solid state is stabilized by a range of intermolecular interactions including O-H⋅⋅⋅O, C-H⋅⋅⋅O, π⋅⋅⋅π and C-H⋅⋅⋅π. Magnetic susceptibility measurements (χT vs T curves) over a wide range of temperature indicate dominant antiferromagnetic interactions between the Cu(II) centres in both complexes, while DFT calculations reveal the nature and amplitude of the main magnetic interactions. Theoretical study further shows strong antiferromagnetic interactions inside the trimeric units of both complexes as well as both weak ferro- and antiferromagnetic interactions among the trimers. The so-obtained J values have been employed to fit the χT vs T curves, using simplified spin models which correctly reproduce the main features of the experimental curves. Thus, this combined experimental and theoretical study provides insight into the magnetic structure of the copper complexes.

Structurally intriguing rearranged bicyclogermacrene-type sesquiterpenoid from Aphania oligophylla

An investigation on the aqueous ethanol extract of the powdered twigs of Aphania oligophylla has afforded a skeletal new sesquiterpenoid aphanoid A (1) and one new aromadendrane-type sesquiterpenoid aphanoid B (2), as well as six known sesquiterpenoids (3–8). Their structures including the absolute configurations were characterized based on spectroscopic data analysis and X-ray crystallography. Compound 1 featuring an unprecedented tricyclo[6.3.1.03,5]dodecane scaffold, is likely rearranged from the bicyclogermacrene-type sesquiterpenoid. Among those compounds, 2 at 10 μL showed moderate antimalarial effect.

In-silico antibacterial activity of piperazinyl-based copper(II) metallo-organic pharmacophores

The piperazinyl-based Cu(II)-Schiff base complex {[Cu(HL1′)(N3)]2∙(ClO4)2·4H2O} (1) [HL1′ is the Zwitter ionic form of (E)-2-((2-piperazin-1-ylethylimino)methyl)phenol] was synthesized and characterized by spectroscopic and single crystal X-ray diffraction studies. The X-ray single crystal structure analysis shows that the asymmetric unit of 1 contains a four-coordinate discrete complex cation, [Cu(HL1′)(N3)]+ (1a), with a perchlorate anion and a lattice water molecule. Two square planar units of 1a are dimerized by weak Cu···N intermolecular interaction, forming [Cu(HL1′)(N3)]2 2+ (1′a). DFT and TD-DFT calculations of the monomeric cationic unit, [Cu(HL1′)(N3)]+ (1a) were performed. In-silico antibacterial activities of HL1 as well as monomeric and dimeric cationic units 1a and 1'a, respectively, were performed and study shows that 1a (EC50 0.30 μM) and 1′a (EC50 0.06 μM) may be treated as antibacterial drugs after in-vivo analysis and clinical testing.