Thiadiazole derivatives as New Class of β-glucuronidase inhibitors

Thiadiazole derivatives 1–24 were synthesized via a single step reaction and screened for in vitro β-glucuronidase inhibitory activity. All the synthetic compounds displayed good inhibitory activity in the range of IC₅₀ = 2.16 ± 0.01–58.06 ± 1.60 μM as compare to standard d-saccharic acid 1,4-lactone (IC₅₀ = 48.4 ± 1.25 μM). Molecular docking study was conducted in order to establish the structure–activity relationship (SAR) which demonstrated that thiadiazole as well as both aryl moieties (aryl and N-aryl) involved to exhibit the inhibitory potential. All the synthetic compounds were characterized by spectroscopic techniques ¹H, ¹³C NMR, and EIMS.     

Antioxidant prenylated phenols of Artocarpus plants attenuate ultraviolet radiation-induced damage on human keratinocytes and fibroblasts

Two novel prenylated phenols, cyclocomunoindenol (1) and cyclocomunohexanol (2) were isolated from the cortex of roots of Artocarpus communis. Their structures were determined by spectroscopic methods. Compounds 2 and 6 revealed significant DPPH-scavenging activity with an IC₅₀ values of 435.48 ± 0.93 and 53.55 ± 8.73 μM, respectively. Compounds 1, 2, and 6 displayed significant ABTS⁺ scavenging activity with an IC₅₀ values of 164.26 ± 2.44, 227.01 ± 3.64, and 44.09 ± 0.88 μM, respectively. Compound 6 exhibited an inhibitory effect on XO activity with an IC₅₀ value of 10.91 ± 1.77 μM and the relative oxygen radical absorbance capacity (ORAC) values of 1–6, using ORAC-pyrogallol red (PGR) assay, were determined to be 0.28 ± 0.06, 0.31 ± 0.02, 0.55 ± 0.25, 0.84 ± 0.36, 0.35 ± 0.15, and 0.70 ± 0.09, respectively. Antioxidants 5 and 6 significantly attenuate UVA radiation-induced damage on human HaCaT keratinocytes and Hs68 fibroblasts. These finding showed that 1–6 may be used as antioxidants and 5 and 6 may protect skin against the adverse effects of UV radiation.     

Hydrothermal syntheses and characterizations of two novel heteropolytungstate supported coordination compounds

Two novel heteropolytungstates, [Ni(2,2′-bpy)₃]_1.5{PW_10.79V_1.21O₄₀(VO)_0.5[Ni(2,2′-bpy)₂L]} · 0.5H₂O (1) (2,2′-bpy = 2,2′-bipyridine, L = 0.5H₂O + 0.5OH^?) and K[PW₁₂O₄₀[Ni(1,10-phen)₂(OH)]₂] · 2H₂O (2) (1,10-phen = 1,10-phenanthroline), have been synthesized under hydrothermal conditions and characterized by IR, XPS, and X-ray diffraction analyses. The polyoxoanion of 1 is a mono-capped α-Keggin cluster which supports a metal coordination fragment [Ni(2,2′-bpy)₂L]^1.5+, while the structure of 2 exhibits a 1D chain constructed from pseudo-Keggin cluster bi-supported transition metal complexes linked by K⁺ ions. Studies of magnetic properties indicated the presence of paramagnetic behaviours for compounds 1 and 2.     

Solvatomorphs of dimeric transition metal complexes based on the V4O12 cyclic anion as building block: Crystalline packing and magnetic properties

Dinuclear [{M(phen)₂}₂V₄O₁₂] · C₆H₁₂O · H₂O (M = Co^II 1, Mn^II 2, Ni^II 3 and Cu^II 4) and [{Cu(phen)₂}₂V₄O₁₂] · 3.5H₂O 5 has been prepared by biphasic and hydrothermal syntheses, respectively. All five structures exhibit the {V₄O₁₂}^4? cluster in a chair-like configuration, covalently bonded to two [M(phen)₂]²⁺ fragments, producing a super-exchange magnetic phenomenon. The magnetic study of complexes 1–5 shows that they are very weak antiferromagnetically coupled systems, with J values of ?0.14, 2; ?0.64, 3 and ?0.23, 4 cm^?1. Complexes 1 to 3 correspond to isostructural compounds in which the cyclovanadate group acts as a bidentate bridged ligand. In the copper complexes (4 and 5) the {V₄O₁₂}^4? anion presents the novel monodentate bridging mode, and therefore a more significant distortion from the chair-like configuration. The mentioned complexes, together with that reported in the literature, permit to conclude that it is quite common for a single molecular species to exist in more than one crystalline arrangement. A detailed analysis of the structures of 1–4 shows that the crystal symmetry cannot be strictly centrosymmetric, due to the presence of the cyclohexanol molecule with a single –OH group in the lattice.     

Acetato complexes of molybdenum(V): A novel tetranuclear core based on the metal–metal bonded {Mo2O4}2+ units

A series of acetato complexes of molybdenum(V), based on the singly metal–metal bonded {Mo₂O₄}²⁺ structural fragment, has been prepared. A dinuclear (PyH)₃[Mo₂O₄Cl₄(OOCCH₃)] · CH₃CN (1) (PyH⁺ = pyridinium cation, C₅H₅NH⁺) was obtained upon the reaction of (PyH)₅[MoOCl₄(H₂O)]₃Cl₂ with the equimolar solution of pyridine and acetic acid in acetonitrile at ambient conditions. The acetato ligand in 1 is coordinated to a pair of molybdenum atoms in a syn–syn bidentate bridging manner. (PyH)_n[MoOBr₄]_n afforded in an analogous synthetic procedure a tetranuclear cluster, [Mo₄O₈(OOCCH₃)₃(OH)Py₄] · 1/2CH ₃CN · 1/2H₂O (3), with a novel core which may be envisioned as the acetate- and hydroxide-assisted assembly of {Mo₂O₄}²⁺ building blocks. Its structure is presented in terms of known tetranuclear clusters which are also composed of two {Mo₂O₄}²⁺ units. The acetato ligands in 3 adopted apart from bidentate bridging binding modes also a monodentate one. Partial substitution of chlorido ligands in (PyH)₃[Mo₂O₄Cl₄(OOCCH₃)] · CH₃CN (1) with pyridine resulted in a neutral [Mo₂O₄Cl(OOCCH₃)Py₃] · PrⁱOH · Py (2) which retained the original acetate coordination. The title compounds were fully characterized by X-ray diffraction studies and infrared vibrational spectroscopy.     

Design,synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi

In this study, we designed and synthesized a series of thiophen-2-iminothiazolidine derivatives from thiophen-2-thioureic with good anti-Trypanosoma cruzi activity. Several of the final compounds displayed remarkable trypanocidal activity. The ability of the new compounds to inhibit the activity of the enzyme cruzain, the major cysteine protease of T. cruzi, was also explored. The compounds 3b, 4b, 8b and 8c were the most active derivatives against amastigote form, with significant IC₅₀ values between 9.7 and 6.03 μM. The 8c derivative showed the highest potency against cruzain (IC₅₀ = 2.4 μM). Molecular docking study showed that this compound can interact with subsites S1 and S2 simultaneously, and the negative values for the theoretical energy binding (E_b = −7.39 kcal·mol⁻¹) indicates interaction (via dipole–dipole) between the hybridized sulfur sp³ atom at the thiazolidine ring and Gly66. Finally, the results suggest that the thiophen-2-iminothiazolidines synthesized are important lead compounds for the continuing battle against Chagas disease.     

Synthesis,structures and characterization of the dinuclear nickel(II) complexes containing N,N,N′,N′-tetrakis[(1-ethyl-2-benzimidazolyl)methyl]-2-hydroxy-1,3-diaminopropane and an azide ion

Two dinuclear nickel(II) complexes, [Ni₂(L-Et)(N₃)(H₂O)₃](NO₃)₂ · 2H₂O (1) and [Ni₂(L-Et)(μ-1,3-N₃)(H₂O)₂](NO₃)₂ · 4H₂O (2) containing (HL-Et = N,N,N′,N′-tetrakis[(1-ethyl-2-benzimidazolyl)methyl]-2-hydroxy-1,3-diaminopropane), have been synthesized and characterized by their IR and UV–Vis spectra and magnetic susceptibilities. The crystal structures of [Ni₂(L-Et)(N₃)(H₂O)₃](NO₃)₂ · CH₃OH (1′) and [Ni₂(L-Et)(μ-1,3-N₃)(H₂O)₂](NO₃)₂ · 2C₂H₅OH (2′) similar to 1 and 2 were determined by X-ray crystallography. In 1′, the two nickel(II) ions are bridged by only an alkoxo group of L-Et⁻, while an azido and an alkoxo connect two nickel(II) ions in 2′. Magnetic susceptibility measurements (2–300 K) showed a weak ferromagnetic exchange coupling between the two nickel(II) ions (2J = 10.1 cm⁻¹) for 1. On the other hand, antiferromagnetic interactions were observed for 2 (2J = −15.8 cm⁻¹).     

Magnetostructural correlations and catecholase-like activities of μ-alkoxo-μ-carboxylato double bridged dinuclear and tetranuclear copper(II) complexes

Two μ-alkoxo-μ-carboxylato bridged dinuclear copper(II) complexes, [Cu₂(L¹)(μ-HCO₂)] (1) ((H₃L¹ = 1,3-bis(5-bromosalicylideneamino)-2-propanol)), [Cu₂(L²)(μ-HCO₂)] · dmf (2) (H₃L² = 1,3-bis(3,5-chlorosalicylideneamino-2-propanol)), and two μ-alkoxo-μ-dicarboxylato doubly bridged tetranuclear copper(II) complexes, [{Cu₂(L³)}₂(μ-O₂C–C(CH₃)₂–CO₂)] · 5H₂O · 3CH₃OH (3) ((H₃L³ = 1,3-bis(salicylid-deneamino)-2-propanol)) and [{Cu₂(L³)}₂(μ- O₂CCH₂–C₆H₄–CH₂CO₂)] · 2H₂O (4) have been prepared and characterized. The single crystal X-ray analysis shows that the structures of complexes 1 and 2 are dimeric with two adjacent copper(II) atoms bridged by μ-alkoxo-μ-carboxylato ligands with the Cu⋯Cu distances and Cu–O(alkoxo)–Cu angles are 3.511 Å and 132.85° for 1, 3.517 Å and 131.7° for 2, respectively. Complexes 3 and 4 consist of μ-alkoxo-μ-dicarboxylato doubly bridged tetranuclear Cu(II) complexes with mean Cu–Cu distances and Cu–O–Cu angles of 3.158 Å and 108.05° for 3 and 3.081 Å and 104.76° for 4, respectively. Magnetic measurements reveal that 1 and 2 are strong antiferromagnetically coupled with 2J = −156 and −152 cm⁻¹, respectively, while 3 and 4 exhibit ferromagnetic coupling with 2J = 86 and 155.2 cm⁻¹, respectively. The 2J values of 1–4 are linearly correlated to the Cu–O–Cu angles. Dependence of the pH at 25 °C on the reaction rate of oxidation of 3,4-di-tert-butylcatechol (3,5-dtbc) to the corresponding quinone catalyzed by 1–4 was studied. Complexes 1–4 exhibit high catecholase-like activity at pH 9.0 and 25 °C for oxidation of 3,5-di-tert-butylcatechol.     

Expanding the 4,4′-bipyridine ligand: Structural variation in {M(pytpy)2}2+ complexes (pytpy = 4′-(4-pyridyl)-2,2′:6′,2″-terpyridine,M = Fe,Ni, Ru) and assembly of the hydrogen-bonded,one-dimensional polymer {[Ru(pytpy)(Hpytpy)]}n3n+

The solid state structures of [Ni(1)₂][NO₃]₂ · 2MeOH · 2H₂O, [Fe(1)₂][ClO₄]₂ · 2MeOH · 0.5H₂O, [Ru(1)₂][PF₆]₂ and [Ru(1)₂][PF₆][NO₃] (1 = 4′-(4-pyridyl)-2,2′:6′,2″-terpyridine) are presented and the structural variation observed for the {M(1)₂}²⁺ unit is discussed. Protonation of the pendant pyridine group in [Ru(1)₂]²⁺ leads to the formation of a hydrogen-bonded, one-dimensional polymer [{Ru(1)(H1)}_n]³ⁿ⁺ exemplifed by the solid-state structure of [{Ru(1)(H1)}{Fe(NCS)₆} · 1.25H₂O]_n.     

Synthesis and in silico studies of novel sulfonamides having oxadiazole ring: As β-glucuronidase inhibitors

Novel sulfonamides having oxadiazole ring were synthesized by multistep reaction and evaluated to check in vitro β-glucuronidase inhibitory activity. Luckily, except compound 13, all compounds were found to demonstrate good inhibitory activity in the range of IC₅₀ = 2.40 ± 0.01–58.06 ± 1.60 μM when compared to the standard d-saccharic acid 1,4-lactone (IC₅₀ = 48.4 ± 1.25 μM). Structure activity relationship was also presented. However, in order to ensure the SAR as well as the molecular interactions of compounds with the active site of enzyme, molecular docking studies on most active compounds 19, 16, 4 and 6 was carried out. All derivatives were fully characterized by ¹H NMR, ¹³C NMR and EI-MS spectroscopic techniques. CHN analysis was also presented.     

Triazinoindole analogs as potent inhibitors of α-glucosidase: Synthesis,biological evaluation and molecular docking studies

A new series of triazinoindole analogs 1–11 were synthesized, characterized by EI-MS and ¹H NMR, evaluated for α-glucosidase inhibitory potential. All eleven (11) analogs showed different range of α-glucosidase inhibitory potential with IC₅₀ value ranging between 2.46 ± 0.008 and 312.79 ± 0.06 μM when compared with the standard acarbose (IC₅₀, 38.25 ± 0.12 μM). Among the series, compounds 1, 3, 4, 5, 7, 8, and 11 showed excellent inhibitory potential with IC₅₀ values 2.46 ± 0.008, 37.78 ± 0.05, 28.91 ± 0.0, 38.12 ± 0.04, 37.43 ± 0.03, 36.89 ± 0.06 and 37.11 ± 0.05 μM respectively. All other compounds also showed good enzyme inhibition. The binding modes of these analogs were confirmed through molecular docking.     

Synthesis,in vitro evaluation and molecular docking studies of biscoumarin thiourea as a new inhibitor of α-glucosidases

Biscoumarin analogs 1–18 have been synthesized, characterized by EI-MS and ¹H NMR and evaluated for α-glucosidase inhibitory potential. All compounds showed variety of α-glucosidase inhibitory potential ranging in between 13.5 ± 0.39 and 104.62 ± 0.3 μM when compared with standard acarbose having IC₅₀ value 774.5 ± 1.94 μM. The binding interactions of the most active analogs were confirmed through molecular docking. The compounds showed very good interactions with enzyme. All synthesized compounds 1–18 are new. Our synthesized compounds can further be studied to developed lead compounds.     

Synthesis of novel pyrazole–thiadiazole hybrid as potential potent and selective cyclooxygenase-2 (COX-2) inhibitors

A series of 1,3,4-trisubstituted pyrazole derivatives (3a–f), (4a–f), and (5a–f) have been synthesized and evaluated for their cyclooxygenase (COX-1 and COX-2) inhibitory activity. The structures of newly synthesized compounds were characterized by IR, ¹H NMR, and mass spectral analysis. All of the compounds showed good inhibition of COX-2 with IC₅₀ of 1.33–17.5 μM. Among these derivatives, compound (5c) was the most potent and selective COX-2 inhibitor (IC₅₀ = 1.33 μM), with a significant selectivity index (SI >60). Molecular docking studies were carried out in order to predict the hypothetical binding mode of these compounds to the COX-2 isoenzyme. The result of present study suggests that pyrazole–thiadiazole hybrid could be an interesting approach for the design of new selective COX-2 inhibitory agents.     

Active compounds from a diverse library of triazolothiadiazole and triazolothiadiazine scaffolds: Synthesis,crystal structure determination,cytotoxicity, cholinesterase inhibitory activity,and binding mode analysis

In an effort to identify novel cholinesterase candidates for the treatment of Alzheimer’s disease (AD), a diverse array of potentially bioactive compounds including triazolothiadiazoles (4a–h and 5a–f) and triazolothiadiazines (6a–h) was obtained in good yields through the cyclocondensation reaction of 4-amino-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thiol (3) with various substituted aryl/heteroaryl/aryloxy acids and phenacyl bromides, respectively. The structures of newly prepared compounds were confirmed by IR, ¹H and ¹³C NMR spectroscopy and, in case of 4a, by single crystal X-ray diffraction analysis. The purity of the synthesized compounds was ascertained by elemental analysis. The newly synthesized conjugated heterocycles were screened for cholinesterase inhibitory activity against electric eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE). Among the evaluated hybrids, several compounds were identified as potent inhibitors. Compounds 5b and 5d were most active with an IC₅₀ value of 3.09 ± 0.154 and 11.3 ± 0.267 μM, respectively, against acetylcholinesterase, whereas 5b, 6a and 6g were most potent against butyrylcholinesterase, with an IC₅₀ of 0.585 ± 0.154, 0.781 ± 0.213, and 1.09 ± 0.156 μM, respectively, compared to neostigmine and donepezil as standard drugs. The synthesized heteroaromatic compounds were also tested for their cytotoxic potential against lung carcinoma (H157) and vero cell lines. Among them, compound 6h exhibited highest antiproliferative activity against H157 cell lines, with IC₅₀ value of 0.96 ± 0.43 μM at 1 mM concentration as compared to vincristine (IC₅₀ = 1.03 ± 0.04 μM), standard drug used in this study.     

Structural and antitumor activity study of γ-octamolybdates containing aminoacids and peptides

γ-Type octamolybdates of the formulae, Na₄[Mo₈O₂₆(alaO)₂] · 18H₂O (I), Na₄[Mo₈O₂₆(glyglyO)₂] · 15H₂O (II) and Na₄[Mo₈O₂₆(glyglyO)₂] · 12H₂O (III) have been prepared from sodium molybdate in aqueous solution by adding dl-alanine or glycylglycine. Their crystal structures have been determined by X-ray structure analysis. dl-alanine and glycylglycine coordinate molybdenum atom in γ-octamolybdate [Mo₈O₂₆]⁴⁻ anions via monodentate carboxylate-oxygen atom. The prepared octamolybdates were screened for the possible antiproliferative activity on a panel of five tumor cell lines and on a normal cell line. All tested compounds showed a differential cell-growth inhibition in a dose-dependent manner selectively on hepatocellular carcinoma cell line (HepG2) and breast cancer cell line (MCF-7).     

Design,synthesis and biological evaluation of heterocyclic azoles derivatives containing pyrazine moiety as potential telomerase inhibitors

Three series of novel heterocyclic azoles derivatives containing pyrazine (5a–5k, 8a–8k and 11a–11k) have been designed, synthesized, structurally determined, and their biological activities were evaluated as potential telomerase inhibitors. Among the oxadiazole derivatives, compound 5c showed the most potent biological activity against SW1116 cancer cell line (IC₅₀ = 2.46 μM against SW1116 and IC₅₀ = 3.55 μM for telomerase). Compound 8h performed the best in the thiadiazole derivatives (IC₅₀ = 0.78 μM against HEPG2 and IC₅₀ = 1.24 μM for telomerase), which was comparable to the positive control. While compound 11f showed the most potent biological activity (IC₅₀ = 4.12 μM against SW1116 and IC₅₀ = 15.03 μM for telomerase) among the triazole derivatives. Docking simulation by positioning compounds 5c, 8h and 11f into the telomerase structure active site was performed to explore the possible binding model. The results of apoptosis demonstrated that compound 8h possessed good antitumor activity against HEPG2 cancer cell line. Therefore, compound 8h with potent inhibitory activity in tumor growth inhibition may be a potential antitumor agent against HEPG2 cancer cell. Therefore, the introduction of oxadiazole, thiadiazole and triazole structures reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity.     

Synthesis, α-glucosidase inhibitory,cytotoxicity and docking studies of 2-aryl-7-methylbenzimidazoles

Benzimidazole analogs 1–27 were synthesized, characterized by EI-MS and ¹H NMR and their α-glucosidase inhibitory activities were found out experimentally. Compound 25, 19, 10 and 20 have best inhibitory activities with IC₅₀ values 5.30 ± 0.10, 16.10 ± 0.10, 25.36 ± 0.14 and 29.75 ± 0.19 respectively against α-glucosidase. Compound 6 and 12 has no inhibitory activity against α-glucosidase enzyme among the series. Further studies showed that the compounds are not showing any cytotoxicity effect. The docking studies of the compounds as well as the experimental activities of the compounds correlated well. From the molecular docking studies, it was observed that the top ranked conformation of all the compounds fit well in the active site of the homology model of α-glucosidase.     

Design,synthesis, anticancer activity and docking studies of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives as mTOR inhibitors

A series of 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives (7a–q, 10a–q) were designed, synthesized and their chemical structures were confirmed by ¹H NMR, ¹³C NMR, MS and HRMS spectrum. All the compounds were evaluated for the inhibitory activity against mTOR kinase at 10 μM level. Five selected compounds (7b, 7e, 7h, 10b and 10e) were further evaluated for the inhibitory activity against PI3Kα at 10 μM level, and the IC₅₀ values against mTOR kinase and two cancer cell lines. Twelve of the target compounds exhibited moderate antitumor activities. The most promising compound 7e showed strong antitumor activities against mTOR kinase, H460 and PC-3 cell lines with IC₅₀ values of 0.80 ± 0.15 μM, 7.43 ± 1.45 μM and 11.90 ± 0.94 μM, which were 1.28 to 1.71-fold more active than BMCL-200908069-1 (1.37 ± 0.07 μM, 9.52 ± 0.29 μM, 16.27 ± 0.54 μM), respectively. Structure–activity relationships (SARs) and docking studies indicated that the thiopyrano[4,3-d]pyrimidine scaffolds exerted little effect on antitumor activities of target compounds. Substitutions of aryl group at C-4 position had a significant impact on the antitumor activities, and 4-OH substitution produced the best potency.     

Syntheses and crystal structures of trimethyltin(IV) coordination polymers based on mixed ligands of 5-nitroisophthalate and 2,2′(4,4′)-bipy or phen

The trimethyltin(IV) polymer [(Me₃Sn)₂(nip) · EtOH]_n (1) of 5-nitroisophthalic acid (H₂nip) and its three derivatives with mixed organic N-donor ligands 2,2′-bipy [(Me₃Sn)₂(nip) · 2H₂O] · [(Me₃Sn)₂(nip) · H₂O] · 2(2,2′-bipy) (2) 4,4′-bipy {[(Me₃Sn)₂(nip)]₂(4,4′-bipy)}_n (3) or phen [(Me₃Sn)₂(nip) · H₂O] · (phen) (4) have been synthesized by the reaction of trimethyltin(IV) chloride and H₂nip when sodium ethoxide was added in the presence of 2,2′-bipy 4,4′-bipy or phen. All complexes 1–4 were characterized by elemental, IR, ¹H, ¹³C, and ¹¹⁹Sn NMR spectroscopy and X-ray crystallography analyses. Crystal, data collection and structure refinement parameters for complexes 1, 2, 3 and 4 are shown in Table 1, Table 2, respectively. The X-ray data showed the geometries of all the tin atoms in complexes 1–4 are trigonal bipyramidal. The X-ray analysis of 1 showed that the structure was a polymeric infinite chain with neighboring triorganotin centers being linked by dicarboxylate ligands and hydrogen bonds were found between adjacent chains. For 2, two different monomers were found, in one monomer, Me₃Sn were coordinated to both carboxyl groups of the ligand and water molecules were coordinated to the two Sn(IV) centers. In the other monomer, water molecules were coordinated to only one Sn center. Co-crystallized2,2′-bipy was found in 2 and a 2D supermolecular structure was formed via O–H⋯O and O–H⋯N (N atoms derived from 2,2′-bipy) hydrogen bonds. In 3 however, a 2D polymeric block was formed due to the inversion center of the 4,4′-bipy. For 4, due to the O–H⋯O and O–H⋯N (N atoms derived from phen) hydrogen bonds and intermolecular Sn⋯O bonds, a 2D polymeric structure was formed.     

Synthesis,X-ray crystal structure,DNA/protein binding and cytotoxicity studies of five α-aminophosphonate N-derivatives

Five new α-aminophosphonates are synthesized and characterized by EA, FT-IR, ¹H NMR, ¹³C NMR, ³¹P NMR, ESI-MS and X-ray crystallography. The X-ray analyses reveal that the crystal structures of 1–5 are monoclinic or triclinic system with the space group P 21/c, P − 1, P − 1, P2(1)/c and P − 1, respectively. All P atoms of 1–5 have tetrahedral geometries involving two O-ethyl groups, one C_α atom, and a double bond O atom. The binding interaction of five new α-aminophosphonate N-derivatives (1–5) with calf thymus(CT)-DNA have been investigated by UV–visible and fluorescence emission spectrometry. The apparent binding constant (Kapp) values follows the order: 1 (3.38 × 10⁵ M⁻¹) > 2 (3.04 × 10⁵ M⁻¹) > 4 (2.52 × 10⁵ M⁻¹) > 5 (2.32 × 10⁵ M⁻¹) > 3 (2.10 × 10⁵ M⁻¹), suggesting moderate intercalative binding mode between the compounds and DNA. In addition, fluorescence spectrometry of bovine serum albumin (BSA) with the compounds 1–5 showed that the quenching mechanism might be a static quenching procedure. For the compounds 1–5, the number of binding sites were about one for BSA and the binding constants follow the order: 1 (2.72 × 10⁴ M⁻¹) > 2 (2.27 × 10⁴ M⁻¹) > 4 (2.08 × 10⁴ M⁻¹) > 5 (1.79 × 10⁴ M⁻¹) > 3 (1.17 × 10⁴ M⁻¹). Moreover, the DNA cleavage abilities of 1 exhibit remarkable changes and the in vitro cytotoxicity of 1 on tumor cells lines (MCF-7, HepG2 and HT29) have been examined by MTT and shown antitumor effect on the tested cells.