Synthesis,bioactivity, action mode and 3D-QSAR of novel anthranilic diamide derivatives

Several newly synthesized anthranilic diamide derivatives were found to exhibit excellent bioactivity. The action mode test and 3D-QSAR analysis provided valuable information for evaluation and future design of anthranilic diamide insecticides.     

Design,synthesis, and fungicidal activity of novel 1,3,4-oxadiazole derivatives

Employing the intermediate derivatization method (IDM), a series of 1,3,4-oxadiazole derivatives containing arylpyrazoloxyl moiety were designed and synthesized. In vitro bioassays showed that these compounds have moderate to significant fungicidal activity against rice sheath blight and sorghum anthracnose. Furthermore, compound 20 is a promising fungicide for further development.     

Palladium-catalyzed domino sequence for the synthesis of N-aryl quinolinone-3-carboxylate derivatives and their anti-proliferative activity

An efficient and an operationally simple Palladium-catalyzed domino reaction for the synthesis of N-aryl quinolinone-3-carboxylate derivatives has been developed via the reaction between diethyl 2-(2-bromobenzylidine) malonate and anilines. These newly synthesized compounds exhibited good to moderate anti-proliferative activity with GI₅₀ values ranging from 0.41 µM to 45.77 µM. Among them, compounds 6j, 6k and 6m demonstrated potential activity particularly against MCF-7 (breast) and KB (oral) cancer cell lines.     

Synthesis and in vitro biology of Co(II), Ni(II), Cu(II) and Zinc(II) complexes of functionalized beta-diketone bearing energy buried potential antibacterial and antiviral O,O pharmacophore sites

The clinically active functionalized β-diketones 1-(2′,4′-dihydroxyphenyl)-3-(2″-substitutedphenyl)-propane-1,3-dione (L₁)–(L₂) have been synthesized from Baker–Venkataraman transformation of 2,4-diaroyloxyacetophenones. Their transition metal complexes (1)–(8) have been prepared and characterized by physical, spectral and analytical data. The functionalized beta-diketone potentially acts as bidentate ligand and co-ordinate with the transition metal atom through beta-diketo system. The complexes have general formula [ML₂] where M = Co(II), Ni(II), Cu(II), Zinc(II) and L = ligand. The 1-(2′,4′-dihydroxyphenyl)-3-(2″-substitutedphenyl)-propane-1,3-dione and their transition metal complexes have been screened for in vitro antibacterial, antifungal and antioxidant bioassay. The biological activity data show that the transition metal complexes are more potent antibacterial, antifungal and antioxidant agents than the parent functionalized beta-diketone against different bacterial and fungal species. This constitutes a new group of compounds that can be used as potential metal derived drugs. Ultimately, here we can prompt about the use of metals for the drugs. The metal complexes were also studied for their thermogravimetric analyses.     

Synthesis of 5-{[(1Hbenzo[d]imidazol-2-yl)sulfonyl]methyl}-3-phenyl-4,5-dihydroisoxazole derivatives,invitro antibacterial and antioxidant studies along with their insilico analyses

Synthesis of a series of novel sulfone derivatives 6(a-u) possessing benzimidazoles and isoxazoline rings tailored in a single molecule 5(a-u) was done by reactions using 5-(bromomethyl)-3-phenyl-4,5-dihydroisoxazoles 3(a-u) and 5-{[(1H-benzo[d]imidazol-2-yl)thio]methyl}-3-phenyl-4,5-dihydroisoxazoles 4(a-u) molecules. The chemical structures of all the newly synthesized compounds were established by IR, ¹HNMR, ¹³CNMR and LCMS spectral data. The biological characteristics of the novel sulfone compounds, such as their antioxidant and antibacterial activity, were evaluated. Among the synthesized sulfones derivatives, compounds 6 g, 6b, and 6e demonstrated outstanding antibacterial activity while compounds 6b, 6c, 6i, 6j, and 6 k demonstrated higher antioxidant activity. Further insilico absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies of synthesized sulfones were studied which exhibited excellent intestinal absorption which is more than 80 %, and relatively moderate toxicity. Molecular docking studies confirmed the antibacterial and antioxidant potential which is comparable with the standard.     

Synthesis and antiviral bioactivity of novel chalcone derivatives containing purine moiety

A series of novel chalcone derivatives containing purine group was synthesized and evaluated for their antiviral activities against cucumber mosaic virus and tobacco mosaic virus. Compound 3o exhibited remarkable antiviral activities and strong combining capacity to tobacco mosaic virus coat protein.     

Synthesis and antimicrobial activities of novel quinazolin-4(3H)-one derivatives containing a 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole moiety

A series of novel quinazolin-4(3H)-one derivatives (6a–6y) containing a 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole moiety were designed and synthesized, and their structures were fully characterized by ¹H NMR, ¹³C NMR, HRMS and IR spectra. Among them, the structure of compound 6u was unambiguously confirmed via single crystal X-ray diffraction analysis. The obtained bioassay results showed that compounds 6h, 6k, 6l and 6y had the EC₅₀ (half-maximal effective concentration) values of 34.8, 28.2, 41.5 and 42.5 μg/mL against the phytopathogenic bacterium Xanthomonas oryzae pv. oryzae (Xoo), respectively, which were significantly better than commercial bactericide Bismerthiazol (EC₅₀ = 95.8 μg/mL). Additionally, compounds 6a and 6b exhibited the strong inhibition activity against the pathogen Xanthomonas axonopodis pv. citri (Xac).     

Antiplasmodial Securinega alkaloids from Phyllanthus fraternus: Discovery of natural (+)-allonorsecurinine

The chemical investigation of the antimalarial plant Phyllanthus fraternus G. L. Webster (Phyllanthaceae) resulted in the discovery of the Securinega alkaloid (+)-allonorsecurinine (1), previously reported as a synthetic compound, together with the known ent-norsecurinine (2), nirurine (3), bubbialine (4), epibubbialine (5) and the lignan phyllanthin (6). The structure and absolute configuration of the new compound were elucidated on the basis of extensive spectroscopic analysis, optical rotation, and GIAO NMR shift calculation followed by CP3 analysis. The antiplasmodial activity of these compounds was evaluated against chloroquine-resistant (W2) and -sensitive (3D7) strains of Plasmodium falciparum. Among them, ent-norsecurinine (2) and (+)-allonorsecurinine (1) showed the strongest activity (IC₅₀: 1.14 ± 0.32 and 2.57 ± 0.53 µM) respectively, against W2 but one of the weakest against 3D7.     

Synthesis,insecticidal activities and SAR studies of novel anthranilic diamides containing trifluoroethoxyl substituent and chiral amino acid moieties

Based on the structures of ryanodine receptors (RyRs) activators anthranilic diamide insecticidal agents and FKI- 1033, a series of 18 novel trifluoroethoxyl-containing chiral anthranilic diamides Ia–i and IIa–i were synthesized. Their insecticidal activities were evaluated systematically and the SAR was discussed.     

Synthesis,biological evaluation and Structure Activity Relationships (SARs) study of 8-(substituted)aryloxycaffeine

A series of 8-(substituted)aryloxycaffeine were prepared from 8-bromocaffeine and (substituted)phenols by modified Ullmann reaction. In vitro antibacterial activity, inhibitory activity on topoisomerase II and pharmacological activities were evaluated for the synthesized 8-(substituted)aryloxycaffeine. Among the synthesized compounds, 8-(5-chloropyridin-3-yloxy)caffeine (3k) showed strong inhibitory activity (MIC = 15.6 μg/mL) against the tested gram negative (−) bacteria Salmonella enteritidis. 8-(quinolin-8-yloxy)caffeine (3g) showed the strongest inhibitory activity against topoisomerase II. And the compounds 8-(6-methylpyridin-2-yloxy)caffeine (3j) and 8-(3-chloro-6-(trifluoromethyl)pyridin-2-yloxy)caffeine (3m) showed analgesic effect without the central nervous system stimulation.     

Cytotoxic arylbenzofuran and stilbene derivatives from the twigs of Artocarpus heterophyllus

Four new natural products, including three arylbenzofurans named heterophyllenes A-C (1–3), and one stilbene named heterophyllene D (4), together with twenty-one known compounds were isolated from the twigs of Artocarpus heterophyllus and their structures elucidated by spectroscopic methods, mainly 1D and 2D NMR spectroscopy. The cytotoxic activity of selected compounds against KB, MCF-7 and NCI-H187 cell lines was evaluated. Heterophyllene C (3) exhibited cytotoxicity against the MCF-7 cell line with an IC₅₀ value of 12.56 μM. Additionally, the known compounds norartocarpin and artocarpin showed cytotoxic activity against MCF-7 and KB cell lines with IC₅₀ values of 10.04 and 13.57 μM, respectively. Both compounds also displayed cytotoxicity against the NCI-H187 cell line with values of 14.78 and 14.21 μM, respectively.     

Porous CuO catalysed green synthesis of some novel 3-alkylated indoles as potent antitubercular agents

A green multicomponent one pot synthesis of novel 2-(1H-indol-3-ylmethyl)-5,5-dimethyl-cyclohexane-1,3-diones (4a–l) in excellent yields was conveniently carried out in aqueous medium at room temperature over mpCuO as heterogeneous catalyst. The synthesised 3-alkylated indoles were characterised by FTIR, ¹H NMR, ¹³C NMR and HRLCMS. The nanocatalyst was facially synthesised via a green sol–gel route and characterised by SEM, TEM, EDX, PXRD, BET and FTIR. The porous nanocatalyst can be recycled five times without significant drop in product yield. Docking studies against enoyl acyl carrier protein reductase predicts that the compounds bind at the active site with high binding affinity values. The compound 4k (MIC, 15 μg/mL) shows comparable activity in reference to Isoniazid at the same concentrations against MT H37 Rv.     

Two new tetrahydrofuran derivatives from the fungus Mucor spp. SNB-VECD11D isolated from the Chrysomelidae Acalymma bivittula

Two new tetrahydrofuran derivatives, mucorinic acids A (1) and B (2) as well as the three known secondary metabolites dehydroabietic acid (3), Δ8-dihydroabietic acid (4) and 8-pimarenic acid (5) were isolated from a solid culture of the fungus Mucor spp. isolated on insect Acalymma bivittula. The structure of these compounds was elucidated by analysis of NMR and MS spectroscopic data. Compounds were tested in antimicrobial and insecticidal assays. Dehydroabietic acid exhibited moderate larvicidal activity on Aedes aegypti larvae with 65% mortality at 10 ppm. Both new compounds 1 and 2 showed interesting antibacterial activity on Staphylococcus aureus and methicillin resistant S. aureus with MIC values in the 8–16 μg/ml.     

Design,synthesis and biological evaluation of quinazolin-4(3H)-one Schiff base conjugates as potential antiamoebic agents

In an effort to develop novel antiamoebic scaffolds having better efficacy than the standard drug metronidazole (IC₅₀ = 1.80 μM) used against Entamoeba histolytica, quinazolin-4(3H)-one Schiff base conjugates were synthesized and evaluated against HM1: IMSS strain of E. histolytica. Out of the thirteen compounds (S2-S14), six compounds (S2, S3, S4, S5, S6 and S11) were found to be better inhibitors than metronidazole and showed low cytotoxicity on HeLa cells, a cervical cancer cell line. The structure of intermediate compound S1 was confirmed by crystal structure studies.     

Synthesis,spectral characterization,theoretical, antimicrobial,DNA interaction and in vitro anticancer studies of Cu(II) and Zn(II) complexes with pyrimidine-morpholine based Schiff base ligand

Novel Cu(II) (1) and Zn(II) (2) complexes with 4-(1-(4-morpholinophenyl)ethylideneamino)pyrimidine-5-carbonitrile) (L) have been synthesized and characterized by various spectroscopic and analytical techniques. DFT (density functional theory) studies result confirms that, LMCT mechanism have been done between L and M(II) ions. The antimicrobial studies indicate that the ligand L and complexes 1 & 2 exhibit higher activity against the E. coli bacteria and C. albicans fungi. The groove binding mode of ligand L and complexes 1 & 2 with CT-DNA have been confirmed by electronic absorption, competitive binding, viscometric and cyclic voltammetric studies. The electronic absorption titration of ligand L and complexes 1 & 2 with DNA have been carried out in different buffer solutions (pH 4.0, 7.0 & 10.0). The K_b values of ligand L and complexes 1 & 2 are higher in acidic buffer at pH 4.0 (K_b = 2.42 × 10⁵, L; 2.8 × 10⁵, 1; 2.65 × 10⁵, 2) and the results revealed that, the interaction of synthesized compounds with DNA were higher in the acidic medium than basic and neutral medium. Furthermore, CT-DNA cleavage studies of ligand L and complexes 1 & 2 have been studied. The in vitro anticancer activities results show that complexes 1 & 2 have moderate cytotoxicity against cancer cell lines and low toxicity on normal cell line than ligand L.     

Ruellia prostrata Poir. activity evaluated by phytoconstituents,antioxidant, anti-inflammatory,antibacterial activity,and in silico molecular functions

Ruellia prostrata Poir. has been used historically as an anti-cancer, wound healing agent and to treat gonorrhea. We aimed to determine the phytochemicals present in ethyl acetate extract of R. prostrata Poir. (EAERP). We sought to determine the antioxidant, anti-inflammatory, and antibacterial activities in vitro, and toxicity properties in vivo. We also analyzed the Prediction of Activity Spectra for Substances (PASS), physicochemical, ADMET, and drug-likeness properties of phytochemicals in EAERP. To determine phytoconstituents, preliminary phytochemical screening and GC–MS were performed, while FT-IR was used to identify functional groups. The antioxidant activity was evaluated using a DPPH scavenging assay, whereas BSA denaturation and RBC hemolysis inhibition were used to assess anti-inflammatory activity. An agar-well-diffusion assay was performed to estimate the antibacterial activity. Brine shrimp lethality bioassay and oral delivery of EAERP of single-dose were performed to determine cytotoxicity and acute toxicity, respectively. The phytochemical screening revealed the presence of phenols, triterpenoids, saponins, steroids, amino acids, and fat and fixed oils. FT-IR analysis of EAERP showed the presence of many functional groups: alcohols/phenols, carboxylic acids, aldehydes, alkanes, esters, amines, amides, aromatic hydrocarbons, sulfoxides, and alkyl halides. GC–MS revealed the presence of 39 phytoconstituents including steroids, consistent with compounds and functional groups found in preliminary screening and FT-IR. EAERP showed dose-dependent antioxidant activity with an IC₅₀ value of 21.402 µg/mL and anti-inflammatory activity with an IC₅₀ value of 20.564 µg/mL in RBC hemolysis inhibition and 21.115 µg/mL in BSA denaturation assays. EAERP also exhibited dose-related antibacterial activity. EAERP exerted cytotoxicity with an LC₅₀ value of 17.619 μg/mL and acute toxicity with an LD₅₀ value of 4095.328 mg/kg without any adverse effects. The PASS server also predicted that the phytoconstituents of EAERP have antioxidant, anti-inflammatory, and antibacterial activities with probable activity (Pa) ranging from 0.310 to 0.717. Analysis of physicochemical, ADMET, and drug-likeness properties revealed the drug-able efficacy and safety of most compounds. The findings of this study indicated that R. prostrata Poir. contains phytoconstituents with potent antioxidant, anti-inflammatory, and antibacterial activities. Taken together, our measurements suggest that R. prostrata Poir. is a prime candidate for further exploration as a potential therapeutic agent.     

Design,synthesis and antimycobacterial activity of novel nitrobenzamide derivatives

We report herein the design and synthesis of a series of novel nitrobenzamide derivatives. Results reveal that many of them display considerable in vitro antitubercular activity. Four N-benzyl or N- (pyridine-2-yl)methyl 3,5-dinitrobenzamides A6, All, Cl and C4 have not only the same excellent MIC values of0.016 μg/mL against both drug-sensitive MTB strain H37 Rv and two drug-resistant clinical isolates as PBTZ169 and the lead 1, but also acceptable safety indices (SI 1500), opening a new direction for further development.     

Synthesis of new substituted benzaldazine derivatives,hydrogen bonding-induced supramolecular structures and luminescent properties

Syntheses of three benzaldazine compounds 1–3 with the general formula Ar₁(CH = N–N = HC)Ar₂ (Ar₁ = Ar₂ = 2-OH-3,5-^tBu₂C₆H₂ (1), Ar₁ = Ar₂ = 2-BrC₆H₄ (2), Ar₁ = ortho-C₆H₄(NHC₆H₃-Me₂-2,6), Ar₂ = C₆H₄F-2 (3)) are described. All compounds were characterized by elemental analysis, ¹H NMR, ¹³C NMR, IR spectroscopy and single-crystal X-ray crystallography. The different supramolecular structures were obtained through different weak interactions (C ? H···O, O ? H···N and π···π interactions for 1; C ? H···Br and Br···Br interactions for 2; C ? H···F and C ? H···N interactions for 3). Compound 1 shows solvent-dependent fluorescent properties with blue to green emission on the increasing of the solvent polarity. Compounds 2, 3 show blue photoluminescence in different solvents.     

Synthesis and anti-inflammatory and antimicrobial activities of some novel 2-methylquinazolin-4(3H)-one derivatives bearing urea,thiourea and sulphonamide functionalities

A variety of novel 2-methylquinazolin-4(3H)-one derivatives (1–29) bearing urea, thiourea and sulphonamide functionalities at position 3 of biological interest have been synthesized and screened for their anti-inflammatory (TNF-α and IL-6) and antimicrobial activities (antibacterial and antifungal). “Biological evaluation study revealed that the compounds 3, 4, 6, 9, 16 and 18 were found to have promising anti-inflammatory activity (up to 62–84% TNF-α and 73–92% IL-6 inhibitory activity) at concentration of 10 μM with reference to standard dexamethasone (75% TNF-α and 84% IL-6 inhibitory activities at 1 μM) and 7, 10, 12, 23, 25 and 28 have antimicrobial activity at MIC of 10–30 μg/mL against selected pathogenic bacteria and fungi.”     

A new cytotoxic salannin-class limonoid alkaloid from seeds of Azadirachta indica A. Juss

Azadiramide A (1), a new salannin-class limonoid alkaloid, inhibits growth of human breast cancer MDA-MB-231 cell line with IC₅₀ value of 2.70±0.63 μmol/L.