Synthesis,crystal structures and spectroscopic properties of two new organotin (IV) complexes and their antiproliferative effect against cancerous and non-cancerous cells

Cancer has become a leading cause of death worldwide, which is responsible for 7.6 million cancer deaths according to GLOBOCAN survey conducted in 2008. The exploration of cis-platin analogues (carboplatin, lobaplatin, nedaplatin, oxaliplatin) and their incorporation to the treatment of cancer patients has further led interest in exploring metal-based anticancer drugs. The current study describes the synthesis of two new tetra-coordinated mono- and tetranuclear organotin(IV) carboxylate complexes and their in vitro anticancer studies. Each one of the complexes (1–2) has been characterized by analytical (micro- and gravimetric analysis) and spectroscopic (FTIR, ¹H, ¹³C, ¹¹⁹Sn-NMR) techniques. Furthermore, molecular structures of 1 and 2 were elucidated using X-ray crystallography. The characterization data showed that the coordination took place via oxygen atoms from the carboxylate anions to generate 1 as an organodistannoxane dimer and 2 as a mononuclear complex. Exceptionally, the NMR spectroscopic and X-ray crystallographic study showed that acetone molecules also took part in crystallizing 2. Both complexes were tested against three cancerous (colon cancer HCT 116, breast cancer MCF 7, leukemia K562) and one non-cancerous (3T3-L1) cell lines. Both complexes showed same IC₅₀ value (0.2 μM) against HCT 116, whereas for the other two cancer cell lines (MCF 7 and K562) and a normal cell line (3T3-L₁), 2 showed results better than 1. Importantly, the complexes showed exceptional activity against MCF 7 and K562 cell lines and the IC₅₀ values were calculated in nanomoles (MCF 7, IC_50s = 86.5 and 53.4 nM; K 562, IC_50s = 22.9 and 49.6 nM for 1 and 2, respectively). Both, 1 and 2, showed IC₅₀ values many times better than the standard drugs (5-FU, Tamoxifen, betulinic acid and cis-platin) used. Compared to cancerous cell lines, the complexes showed mild toxicity against normal cells (3T3-L1). Overall, two remained relatively effective.     

Pectin mediated green synthesis of Fe3O4/Pectin nanoparticles under ultrasound condition as an anti-human colorectal carcinoma bionanocomposite

This work described the one-pot synthesis of apple pectin encapsulated Fe₃O₄ nanoparticles (Fe₃O₄/Pectin NPs) which is prepared by co-precipitation of Fe(II/(III) ions in alkaline solution mediated by pectin under ultrasound condition. This process led to formation of magnetic nanoparticles within the network of pectin. Physicochemical characterization of the as-synthesized Fe₃O₄/Pectin NPs was carried out through electron microscopy (SEM and TEM), energy dispersive X-ray spectroscopy (EDX), vibrating sample magnetometer (VSM) and X-ray diffraction (XRD). The in vitro cytotoxic and anti-colorectal cancer effects of biologically synthesized Fe₃O₄/Pectin NPs against Ramos.2G6.4C10, HCT-8 [HRT-18], HCT 116, and HT-29 cancer cell lines were assessed. The anti-colorectal cancer properties of the Fe₃O₄/Pectin NPs could significantly remove Ramos.2G6.4C10, HCT-8 [HRT-18], HCT 116, and HT-29 cancer cell lines in a time and concentration-dependent manner by MTT assay. The IC₅₀ of the Fe₃O₄/Pectin NPs were 317, 337, 187, and 300 µg/mL against Ramos.2G6.4C10, HCT-8 [HRT-18], HCT 116, and HT-29 cancer cell lines. The antioxidant activity of Fe₃O₄/Pectin NPs was determined by DPPH method. The Fe₃O₄/Pectin NPs showed the high antioxidant activity according to the IC₅₀ value. It seems that the anti-human colorectal cancer effect of recent nanoparticles is due to their antioxidant effects.     

Diazenyl schiff bases: Synthesis,spectral analysis,antimicrobial studies and cytotoxic activity on human colorectal carcinoma cell line (HCT-116)

A series of diazenyl schiff bases have been synthesized by reaction of salicylaldehyde containing azo dyes with various substituted aniline derivatives in the presence of acetic acid as catalyst. The structures of diazenyl derivatives were determined by FTIR, UV–vis, ¹H NMR, ¹³C NMR, CHN analysis, fluorimetric and mass spectroscopic studies. The synthesized derivatives were screened for their in vitro antimicrobial activity against various Gram-positive (S. aureus, B. subtilis, B. cereus), Gram-negative (S. typhi, S. enterica, E. coli, P. aeruginosa) bacterial and fungal (C. albicans, A. niger and A. fumigatus) strains, using cefadroxil (antibacterial) and fluconazole (antifungal) as standard drugs. The diazenyl schiff bases were also screened for their cytotoxicity against human colorectal carcinoma cell line (HCT-116) using 5-fluorouracil as standard drug by Sulforhodamine-B Stain (SRB) assay. The schiff bases exhibited significant activity toward both Gram-positive, Gram-negative bacterial and fungal strains. Most of the synthesized derivatives showed high activity against S. enterica. 4-((2,5-Dichlorophenyl)diazenyl)-2-((3-bromophenylimino)methyl)phenol (SBN-40) was found to be very active against S. aureus, B. cereus and E. coli, with MIC = 0.69 (µM/ml × 10²). The compound 4-((2-bromophenyl)diazenyl)-2-((4-nitrophenylimino)methyl)phenol (SBN-13) possessed comparable activity (IC₅₀ = 7.5 µg/ml) to the standard drug 5-fluorouracil (IC₅₀ = 3.0 µg/ml) against human colorectal carcinoma cell line (HCT-116).     

Bistachybotrysins D and E,one stereoisomeric pair of cytotoxic phenylspirodrimane dimers from Stachybotrys chartarum

Bistachybotrysins D and E (1 and 2), one stereoisomeric pair of phenylspirodrimane dimers, were isolated from Stachybotrys chartarum CGMCC 3.5365. They represent novel phenylspirodrimane dimers with a central [6,5,6]-tricyclic carbon scaffold containing a cyclopentanone core. The structures of 1 and 2 were elucidated through extensive spectroscopic data analysis, and their absolute configurations were characterized by calculated electronic circular dichroism (ECD). Compounds 1 and 2 displayed potent cytotoxic activity against the four human tumor cell lines HCT116, BGC823, Daoy and HepG2 with IC_ (50)values ranging from 6.7 μmol/L to 11.6 μmol/L. Furthermore, a plausible biogenetic pathway for 1 and 2 is proposed.     

Green synthesis of plant-stabilized Au nanoparticles for the treatment of gastric carcinoma

In this study, gold nanoparticles (AuNPs) were green synthesized using plant extract. The obtained nanoparticles (Au NPs) were characterized by advanced physical and chemical techniques like TEM, FTIR, UV–vis, SEM, XRD and EDX. SEM image displayed the quasi-spherical shaped nanoparticles of mean diameter 20–50 nm. All the particles were of uniform shape and texture. From the XRD pattern, four distinct diffraction peaks at 38.2°, 44.2°, 64.7° and 77.4° are indexed as (1 1 1), (2 0 0), (2 2 0) and (3 1 1) planes of fcc metallic gold. The in vitro cytotoxic and anti-gastric carcinoma effects of biologically synthesized Au NPs against cancer cell lines were assessed. The IC₅₀ of the Au NPs were 192, 149, 76 and 85 µg/mL against NCI-N87, MKN45, GC1401 and GC1436 gastric cancer cell lines. The anti-gastric carcinoma properties of the Au NPs could significantly remove the cancer cell lines in a time and concentration-dependent manner. So, the findings of the recent research show that biologically synthesized Au NPs might be used to cure cancer.     

Synthesis,characterization, X-ray diffraction,antimicrobial and in vitro cytotoxicity studies of 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole

The synthesis, spectral characterization, crystal structure and antimicrobial activity of the novel synthetic molecule 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole, C₂₉H₄₈N₄ has been reported. The structure has also been determined by X-ray diffraction technique using direct method and was refined on F² by the full-matrix least-squares. Crystals are orthorhombic and their space group is P212121, with a = 7.230(3), b = 31.451(13), c = 11.974(5) (Å), α = β = γ = 90°. It can be conveniently obtained by the reaction of 7-Oxostigmast-5-ene with hydrazoic acid. The molecule has also been screened for its possible in vitro antimicrobial activity against Staphylococcus aureus, Streptococcus mutans, Streptococcus pyogenes, Staphylococcus epidermidis, Bacillus cereus, Corynebacterium xerosis, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa (MTCC 424). Minimum inhibitory concentration (MIC) of the synthesized compound has also been evaluated. The highest activity is observed against C. xerosi and P. vulgaris. Moreover, the compound has also been screened for its in vitro cytotoxicity against human colon carcinoma cell line, HCT116 and human liver hepatocellular carcinoma cell line, HepG2, using doxorubicin as standard. On the basis of its IC₅₀ values, 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole was found to inhibit the cancer cells effectively.     

A ruthenium(II) complex with the propionate ion: Synthesis,characterization and cytotoxic activity

The complex [Ru(η²-O₂CCH₂CH₃)(dppe)₂]PF₆ (dppe = 1,2-bis(diphenylphosphino)ethane) was prepared and characterized by elemental analysis, spectroscopic techniques, X-ray crystallography, HRESIMS and HRESIMS/MS. The characterization data are consistent with a cis arrangement for the dppe ligands and a bidentate coordination of the propionate ligand through carboxylate oxygens. Cytotoxicity assays were carried out on human and murine cancer and normal cell lines. In general, the [Ru(η²-O₂CCH₂CH₃)(dppe)₂]PF₆ complex was more cytotoxic than both its precursor cis–[RuCl₂(dppe)₂] and the reference metallodrug cisplatin. The best results against the HepG2 human tumour cell line and S180 murine tumour cell line were found with IC₅₀ values of 6.5 ± 0.2 and 0.18 ± 0.03 μM, respectively.     

Phytogenic fabrication of iron oxide nanoparticles and evaluation of their in vitro antibacterial and cytotoxic activity

Several metal-based nanoparticles (NPs) have been found to be toxic and are known to exert adverse health outcomes with irreversible side effects. This highlights the need to discover effective, stable, and biocompatible therapeutic components using natural sources. Here, a hexane extract of Nigella sativa seeds was used to synthesize iron oxide NPs (NS-IONPs) embedded with N. sativa phytoconstituents. The extract acted as a reducing agent that restricted the size of the NS-IONPs to 5–6 nm, signifying the potential to be cleared through the renal system. The fabricated NS-IONPs had a prominent effect on pathogenic gram-negative bacteria, E. coli (19.3 mm) and Salmonella typhi (14.2 mm) and lung cancer cells (lowest IC₅₀ of 18.75 µg/mL) mainly by binding to the phospholipid components of the cell membrane. This resulted in cell shrinkage and further inhibited cell growth. Transmission electron microscopy analyses revealed that the mechanisms of cellular NP uptake varied depending on the cell type. Accumulation of NS-IONPs inside the cell increased BAX expression and arrested the cells at the G0/G1 phase, thereby conspicuously extending the G0 phase to initiate necrosis. Thus, these finding suggest that the synthesized NS-IONPs exhibited high antibacterial activity and effective cytotoxicity against cancer cell lines A549 and HCT116 compared to IONPs. The innovation of the current study is that the biogenic fabrication of IONPs is simple and cost effective results in stable nanomaterial, NS-IONPs with potential antibacterial and anticancer activity, which can be explored furthermore for various biomedical applications.     

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.     

Synthesis,characterization, single crystal XRD,in vitro antimicrobial and cytotoxicity study of tris(ethylenediamine)cobalt(III)chloride oxalate trihydrate

The complex tris(ethylenediamine)cobalt(III)chloride oxalate trihydrate [Co(en)₃]Cl(C₂O₄)·3H₂O crystallizes in the monoclinic space group C₂/c with the following unit cell parameters a = 19.9318 (13), b = 9.3344 (4), c = 19.0881 (13) Å β = 96.846(3)°, Z = 8. The crystal structure was solved by direct methods and refined by full matrix least squares procedures to a final R value of 0.0314 for 4330 observed reflections. The reported cobalt complex is six co-ordinated through amine nitrogen with distorted octahedral geometry. There are uncoordinated chloride and oxalate ions along with the water molecules. In-vitro antimicrobial activity was studied against various test organisms and found to be good. From in-vitro cytotoxic activity of the synthesized complex, the IC₅₀ value was found to be 55.85 μg/ml.     

anti-Tuberculosis natural products: synthesis and biological evaluation of pyridoacridine alkaloids related to ascididemin

There is an urgent need for novel therapeutics possessing new modes of action to treat tuberculosis (TB) infections. In this study we report on the synthesis and biological evaluation of a series of pyrido[2,3,4-kl]acridin-6-one alkaloids related to the anti-TB (MIC 0.35 μM) but cytotoxic (IC₅₀ <0.14 μM) marine natural product ascididemin (1). The most interesting compounds identified were 21 and 24, which were found to inhibit the growth of Mycobacterium tuberculosis (Mtb) H₃₇Rv with MIC 2.0 μM, but with negligible cytotoxicity towards Vero and P388 cells (IC₅₀>25 μM). Another analogue (10) was evaluated against a range of singly-drug-resistant strains of Mtb and was found to exhibit no cross-resistance. These results suggest that the pyrido[2,3,4-kl]acridin-6-one skeleton may provide a useful scaffold for future studies directed towards possible anti-TB drugs.     

Physical properties,biological applications and biocompatibility studies on biosynthesized single phase cobalt oxide (Co3O4) nanoparticles via Sageretia thea (Osbeck.)

Cobalt oxide nanoparticles were successfully biosynthesized by complete green process using aqueous leaf extracts of Sageretia thea as chelating agent. Diverse techniques were applied for characterization. Antibacterial (with and without UV illumination), antileishmanial, antioxidant and enzyme inhibition applications were assessed, while freshly isolated macrophages and red blood cells were used for biocompatibility studies. Good antibacterial nature and enhancement of bactericidal nature upon UV modulation is reported. Staphylococcus aureus and Escherichia coli are indicated as most susceptible bacterial strains. Significant cytotoxic potential is revealed with IC₅₀ calculated as 12.82 µg/ml and 3.16 µg/ml against the axenic leishmanial promastigote and amastigote cultures respectively. Biogenic cobalt oxide nanoparticles indicated DPPH free radical scavenging potential, while moderate antioxidant capacity and reducing power was demonstrated. Bioinspired cobalt oxide also demonstrated alpha amylase and protein kinase inhibition at higher concentrations. Biogenic cobalt oxide was found as more cytotoxic to macrophages (IC₅₀ = 58.55 µg/ml) then to RBC’s (IC₅₀ >200 µg/ml). Our results indicate green synthesis as an alternative, effective and eco-friendly method for the biosynthesis of cobalt oxide nanoparticles with numerous biological applications.     

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 antitumor activities of a new series of 4,5-dihydro-1H-thiochromeno[4,3-d]pyrimidine derivatives

A new series of 4,5-dihydro-1H-thiochromeno[4,3-d]pyrimidine derivatives have been designed and synthesized.The antitumor activities of the target compounds have been evaluated in vitro against two human cancer cell lines including A549 (human alveolar adenocarcinoma cell) and H460 (human lung cancer) by MTT assay.Most of the target compounds exhibited significant antitumor activities against A549 and H460 cancer cell lines.The most potent compound 4-(benzo[d][1,3]dioxol5-yl)-8,9-difluoro-2-(4-methylpiperazin-1-yl)-4,5-dihydro-1H-thiochromeno[4,3-d]pyrimidine (CH05) (IC50=0.44 M,3.07 M) was 2.0 and 8.4 times more active than gefitinib (IC50=0.89 M,16.81 M) against A549 and H460 cell lines,respectively.     

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.     

Hypervalent iodine(III) catalyzed rapid and efficient access to benzimidazoles,benzothiazoles and quinoxalines: Biological evaluation of some new benzimidazole-imidazo[1,2-a]pyridine conjugates

A rapid, simple and highly efficient method for the synthesis of a variety of 2-aryl-benzimidazoles, 2-aryl-benzothiazoles and quinoxalines has been developed using Koser’s reagent [PhI(OH)OTs] as catalyst. The present work highlights the potential of Koser's reagent ([PhI(OH)OTs]) for the synthesis of benzimidazoles, benzothiazoles and quinoxalines, etc. Short reaction time, high yields, importantly low catalyst loading, broad substrate scope and scalability are the salient features of this methodology. Particularly, this method has been employed successfully to synthesize highly structured indole-benzimidazole and quinoxaline-6-carboxamide derivatives as well as biologically important benzimidazole-imidazo[1,2-a]pyridine conjugates in moderate to good yields. These remarkable features make the present methodology a valid contribution to the existing precedents for the synthesis of benzimidazoles, etc. In the MTT assay, benzimidazole-imidazo[1,2-a]pyridine conjugates 3s, 3t and 3v were found to be active on MCF-7 (IC₅₀ values of 5.10 ± 0.10, 8.23 ± 0.02, and 10.75 ± 0.03 µM, respectively) and MDA-MB-231 cell lines (IC₅₀ values of 10.83 ± 0.13, 7.68 ± 0.05, and 7.87 ± 0.24 µM, respectively). Flow-cytometry analysis revealed that the treatment of MCF-7 cells with compound 3s showed moderate effect on the progression of G0/G1 phase of the cell cycle.     

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.     

Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives

The novel 1,4-dihydropyridine derivatives containing the cationic pyridine moiety at the position 4, and the N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle were designed, synthesised, and assessed in biological tests. Among all the novel compounds, the 4-(N-dodecyl) pyridinium group-containing compounds 11 (without the N-propargyl group) and 12 (with the N-propargyl group) demonstrated the highest calcium antagonistic properties against neuroblastoma SH-SY5Y (IC₅₀ about 5–14 μM) and the vascular smooth muscle A7r5 cell (IC₅₀ – 0.6–0.7 μM) lines, indicating that they predominantly target the L-type calcium channels. These compounds showed a slight total antioxidant activity. At concentrations close to those of L-type calcium channel blocking ones, compound 12 did not affect mitochondrial functioning; also, no toxicity was obtained in vivo. The N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle did not essentially influence the compounds’ activity. The 4-(N-dodecyl) pyridinium moiety-containing compounds can be considered as prototype molecules for further chemical modifications and studies as cardioprotective/neuroprotective agents.     

Design, synthesis and antiproliferative activities of novel 5H-pyridazino[4,5-b]indoles

A novel series of 5H-pyridazino[4,5-b]indoles were designed and synthesized in order to find novel potent anticancer compounds.The structures were confirmed by ~1H NMR and MS.Their antiproliferative activities against two cancer cell lines were tested by the MTT method in vitro.Three of compounds (1e,1g,and 1h) exhibited potent antiproliferative activities,especially compound 1h (with IC_(50) values of 5.2μmol/L and 1.9μmol/L against Bel-7402 and HT-1080,respectively).The preliminary structure-activity relationships of 5H-pyridazino[4,5-b]indole derivatives were discussed.     

A new ginsengenin containing an oxacyclopentane-ring isolated from the acid hydrolysate of total ginsenosides

Bioassay-guided fractionation of the acid hydrolysate of total ginsenosides of Panax ginseng C.A.Meyer （Araliaceae） led to the isolation of a novel ginsengenin（1）.The structure of 1 was determined as （20S,22S）-dammar-22,25-epoxy-3β,12β,20-triol by extensive spectroscopy and single-crystal X-ray diffraction analyses.The cytotoxicity of 1 was further tested against SWl 116,HCTl 16,and A549 cells by the MTT method,with IC₅₀ values in the range of 2.96-30.9μmol/L.