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.     

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.     

Two acridones and two coumarins from the roots of Paramignya trimera

Two acridones, paratrimerins C (1) and D (2), and two coumarins, paratrimerins E (3) and F (4), were isolated from the CHCl₃ and EtOAc extracts of Paramignya trimera (Rutaceae), together with twelve known compounds (5–16). Their structures were elucidated on the basis of spectroscopic data. All isolated compounds possessed significant α-glucosidase inhibitory activity in a concentration-dependent manner, and showed more potent inhibitory activity, with IC₅₀ values ranging from 14.6 to 112.2 μM, than the positive control acarbose (IC₅₀, 214.5 μM). The biosynthesis of the isolated coumarins and acridones was proposed.     

Novel dual inhibitors against FP-2 and PfDHFR as potential antimalarial agents: Design,synthesis and biological evaluation

A series of novel 2,4-diaminopyrimidine-modified compounds was designed and synthesized. Compound 14 showed micromolar dual inhibitory effect on both FP-2 and PfDHFR, and potential inhibition to the proliferation of P. falciparum 3D7 strain and chloroquine-resistant P. falciparum Dd2 strain.     

Efficient,collective synthesis and nitric oxide inhibitory activity of rubrolides E,F, R,S and their derivatives

An efficient first synthesis of biologically significant natural butenolides, rubrolides F (1f), R (1r), S (1s) & its 7″,8″-didehydro derivative (1sa), and 3″-bromo rubrolide (1fa) along with the synthesis of rubrolide E (1e) and its di-O-methyl derivative (1ea) is accomplished in a collective fashion from commercially available and inexpensive precursors in overall yields of 14–48.5%. Key features are Wittig-Horner reaction, SeO₂-induced tandem allylic hydroxylation/intramolecular cyclization and Knoevenagel condensation. Next, in their inhibitory activity towards nitric oxide (NO) production in lipopolysaccharide-induced RAW 264.7 macrophages as an indicator of anti-inflammatory activity, all compounds displayed good inhibitory activity in a concentration-dependent manner. None of the compound exhibited notable cytotoxicity at the highest concentration (10 μM) and IC₅₀ values are found in the range from 8.53 to 17.85 μM.     

Diterpenoids from the aerial parts of Leonurus macranthus

One cis clerodane-type (1) and three highly oxygenated labdane-type diterpenes (2-4) were isolated from the aerial parts of Leonurus macranthus. Compound 1 represents the first example of cis clerodane-type diterpene in the plants of Leonurus genus.     

Two new dimmeric xanthanolides isolated from Xanthium mogolium Kitag plant

Two xanthanolide-type dimmers, namely Mogolide D (4) and Mogolide E (5) are isolated from the aerial parts of Xanthium mogolium Kitag plant collected from Heilongjiang province, China. The dimmers’ relative structures are elucidated on the basis of HRESIMS, IR spectrum and NMR spectroscopy. The absolute configurations of them are assigned with ECD spectra. The biosynthetic pathway of the two dimmers is also proposed. Besides, Mogolide D (4) and Mogolide E (5) are tested against MDA-MB-231 breast cancer cell line with IC₅₀ 8.46 μM and 19.20 μM, respectively.     

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.     

Cytotoxic gephyromycins from the Streptomyces sp. SS13I

Two new gephyromycins (1–2), belonging to angucyclinones, were identified from Streptomyces sp. SS13I. Their structures were elucidated by analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and the structure of 1 was further elucidated by X-ray diffraction data. The absolute configurations of compounds 1–2 were evidenced by ECD calculations. To our best knowledge, Compounds 1–2 were the second reported gephyromycin-type angucyclinones. Compound 2 exhibited significant cytotoxicity against PC3 cell lines with IC₅₀ values of 1.38 ± 0.47 μM.     

New compounds from the roots of Coriaria nepalensis

One new sesquiterpene lactone possessing novel variations in the structure, corialactone E (1), one new neolignan, coriarianeolignan A (2), together with three known apocarotenoids (3-5) and one known neolignan (6), have been isolated from a CHCl₃ extract of the roots of Coriaria nepalensis.     

Lanostane triterpenoids from fruiting bodies of the bracket fungus Fomitopsis feei

Three 24-methyl-lanostane triterpenoids, fomitopsins D–F (1–3), were isolated together with four known compounds (4–7) from fruiting bodies of the basidiomycete Fomitopsis feei. The structures were elucidated by spectroscopic analysis and chemical correlations, including the conversion of 1 into a mixture of 2 and 3 under acidic conditions. Compound 1 was previously isolated after conversion to a methyl ester derivative, however, the side-chain stereochemistry was not determined. Fomitopsins E (2) and F (3) exhibited activity against Bacillus cereus with MIC values of 6.25 μg/mL. On the other hand, fomitopsin D (1) showed activity against herpes simplex virus type 1 (HSV-1) with an IC₅₀ value of 17 μg/mL.     

α-Glucosidase inhibitors from the stem of Mangifera reba

Two new neolignans, named rebaneolignan A (1) and B (2), were isolated from the stem of Mangifera reba (Anacardiaceae), together with six known compounds (3–8). Their structures were elucidated on the basis of NMR spectroscopic analysis and the absolute configurations of 1 and 2 were determined by NOESY and CD data. All isolated compounds were found to possess more potent inhibitory activity, with IC₅₀ values ranging from 28.5 to 162.8 µM, than the positive control acarbose (IC₅₀, 214.5 µM). Plausible biosynthetic pathways for the formation of 1 and 2 were proposed based on the oxidative β-5′ coupling reactions.     

Synthesis and molecular modeling study of Cu(Ⅱ) complexes derived from 2-(diphenylmethylene)hydrazinecarbothioamide derivatives with cholinesterase inhibitory activities

Thiosemicarbazones of 2-amino-5-chlorobenzophenone and 3-aminobenzophenone（L¹-L⁴） have been synthesized and their Cu（Ⅱ） complexes（1-4） were afforded via coordination with cupric chloride.All these compounds were characterized by UV-vis and IR spectroscopy together with CHN elemental analysis.NMR spectroscopy was also applied to characterize the ligands.In vitro chohnesterase inhibitory assays for the complexes（1-4） showed IC₅₀ values less than 10μmol/L,with complex 1 exhibiting the most activity,IC₅₀=2.15μmol/L and 2.16μmol/L for AChE and BuChE,respectively. Molecular modeling simulation revealed the binding interaction template for complex 1 with the AChE and BuChE receptors.In DPPH assay,the complexes also showed more in vitro antioxidant activities in comparison to their parent ligands.     

Catharoseumine,a new monoterpenoid indole alkaloid possessing a peroxy bridge from Catharanthus roseus

Catharoseumine (1), a new monoterpenoid indole alkaloid possessing a unique peroxy bridge moiety, was isolated from the whole plants of Catharanthus roseus. Its structure was elucidated on the basis of NMR, IR, UV, and high-resolution mass spectrometric data, and its absolute configuration was determined by ECD and chemical methods. Catharoseumine (1) exhibited cytotoxicity against HL-60 cell line with IC₅₀ value of 6.28 μM and potential inhibition against Plasmodium falciparum falcipain-2 (IC₅₀ = 4.06 μM). A plausible biogenetic pathway of 1 was also proposed.     

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).     

Anticancer and antimicrobial evaluation of newly synthesized steroidal 5,6 fused benzothiazines

A series of new 5α-cholestano [5,6-b] benzothiazines (4–6) has been synthesized by the reaction of 5α-cholestan-6-one (1–3) with 2-aminothiophenol in the presence of iodine. The structures of newly synthesized compounds have been established on the basis of spectral and analytical data. Compounds (1–6) were screened for in vitro anticancer activity against the human cancer cell lines; SW480 (colon adenocarcinoma cells), A549 (lung carcinoma cells), HepG2 (hepatic carcinoma cells) and HeLa (cervical cancer cells) using MTT assay during which the products (4–6) showed marked increase in anticancer activity and in particular, compound 6 showed IC₅₀ = 13.73 μmol L⁻¹ against HeLa cells, being more effective than Doxorubicin against the same cells. Compounds 4 and 6 also showed minimum IC₅₀ of 15.83 μmol L⁻¹ and 16.89 μmol L⁻¹ against HepG2 and A549 cells, respectively. Compounds (1–6) were also tested for in vitro antimicrobial activity against different bacterial as well as fungal strains during which newly synthesized compounds (4–6) were found more potent than starting compounds (1–3). Compound 4 was found to be more potent than the reference drug, Chloramphenicol, in the case of Escherichia coli while compound 5 was found almost equally potential antifungal agent against P. marneffei in comparison with the reference drug, Nystatin.     

Design and synthesis of novel water-soluble amino acid derivatives of chlorin p6 ethers as photosensitizer

Eight new water-soluble amino acid derivatives of chlorin p₆ ethers 6a-h were designed and synthesized using purpurin-18 (2) as key intermediate. All target compounds exhibited better phototoxicity than talaporfin and the most phototoxic compound 6d showed IC₅₀ values of 0.20 μmol/L against A549 cell and 0.41 μmol/L against B16-F10 cell, which represented 31- and 24-fold increase of PDT antitumor efficacy compared to talaporfin.     

Stereoselective synthesis of novel tetrahydroxypyrrolizidines

N-Benzyloxycarbonyl-2,5-dideoxy-2,5-imino-3,4-O-isopropylidene-l-ribose 12a has been converted into (1R,2S,6R,7S,7aS)-5 and (1R,2S,6S,7R,7aR)-1,2,6,7-tetrahydroxypyrrolidin-5-ones 6 and (1R,2S,6S,7S,7aS)-7 and (1R,2S,6R,7R,7aS)-1,2,6,7-tetrahydroxypyrrolizidines 8 following stereoselective paths. These new compounds have been assayed for their inhibitory activities towards 25 glycosidases. Pyrrolizidines 7 and 8 are moderate but selective inhibitors of amyloglucosidase from Rhizopus mold (7: IC₅₀=130 μM, K_i=120 μM; 8: IC₅₀=200 μM, K_i=180 μM, mixed type of inhibition).     

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.     

Synthesis,characterization and cytotoxic investigations of novel bis(indole) analogues besides antimicrobial study

Two series of novel bis(indole) analogues viz., N′-((5-substituted-1H-indol-3-yl)methylene)-n-(1H-indol-3-yl)alkanehydrazides (7a–f) and N′-((5-substituted-1-(3-methylbut-2-enyl)-1H-indol-3-yl)methylene)-n-(1H-indol-3-yl)acetohydrazide (8a–f) were synthesized and characterized by spectral analysis. The target molecules were screened for their antimicrobial, anticancer activities and structure and activity relationship (SAR) was investigated. Compounds 7a, 7c and 8a were found to be active in antimicrobial screening. Anticancer screening reveals that Compound 7c was active against HeLa cell line with an IC₅₀ of 43.1 μM and compound 7d was found to be interesting candidate with an IC₅₀ of 26.0 and 30.2 μM against Colo-205 and Hep G2 cell lines respectively.