A New Rare Halogenated Depside from Lichen and Study of its Anti-Proliferative Activity.

Lichens are a symbiotic association of algae and fungus, belonging to the family Parmeliaceae. Some lichen species are edible and used as an active ingredient for preparation of exotic spices as well as folklore medicine to cure different kinds of ailments. A specimen of lichen was collected from Munner in the Kerala State of South India for chemical profiling. Chemical analyses of the diethyl ether extract of the defatted lichen led to the isolation of six phenols 1-6 with variation of relative abundance. Amongst them, the relative abundance of compound 3 was the greatest (1 % of crude extract) and it was identified as atranorin. The structures of known compounds were confirmed by comparison of their 1H-NMR, 13C NMR, and mass data with published values available in the literature. In vitro bioassay for anti-proliferative activity of these compounds has been conducted against various human cancer cell lines in comparison with paclitaxel as control using SRB assay. Interestingly, a new compound 5 was found along with previously reported compounds from this lichen. This new compound was designated as fluoroatranorin 5 which was reported for the first time herein. The structural characterization of a new depside was determined by spectral methods such as 1H-NMR, 13C NMR, 19F NMR, IR, LC-HRESI-MS, and LC-MS/MS study. Its structure was confirmed by single crystal X-ray diffraction study. This new compound was designated as fluoroatranorin 5 which was reported first time herein. Anti-proliferative activity of all these compounds was evaluated against six different cancer cell lines. The inhibitory activity, IC50 value of compounds 1-3 and 5 exhibited at 99.64, 102.04, 109.20, 53.0 and 2.4 µM on cancer cell lines HT-29 (colon), Hela (cervical), HT-29, HPAC (pancreas) and A2780 (ovarian cancer cell line) respectively in comparison with paclitaxel as control. The new compound 5 exhibited significant activity with IC50 value 2.4 µM on A2780 ovarian cancer cell line.

A novel class of pyrazole analogues as aurora kinase A inhibitor: design, synthesis, and anticancer evaluation.

Pyrazole, as a small molecule, was discovered for higher cytotoxicity and affinity towards Aurora-A kinase. Based on these facts, a novel pyrazole substituted at the 4th position was designed, synthesized, and evaluated against MCF-7, MDA-MB-23, and Vero (non-cancerous kidney cell) cell lines. Compounds5hand5eexhibited greater cytotoxicity in the series against MCF-7 and MDA-MB-231, with GI50 values of 0.12 µM and 0.63 µM, respectively, as compared to Imatinib (GI50 values of 16.08 µM and 10.36 µM). All of the compounds displayed selective cytotoxicity against cancer cells but not on normal Vero cells, supporting the design strategy to be a selective anticancer agent. Furthermore, compounds 5h and 5e inhibited Aurora-A kinase with IC50 values of 0.78 µM (4.70-fold) and 1.12 µM (2.84-fold), respectively, as compared to alisertib (IC50 = 3.36 µM). In addition, compound 5h significantly arrested the cell cycle at G2/M (34.89 %, 5.56-fold) and the apoptotic phase (25.04 %, 11.81-fold) compared to the control. It also triggered an increase in early (7.43 %) and late (14.89 %) phase apoptosis compared to vehicle (0.235 and 0.36 %, respectively), causing 37.89-fold higher total apoptosis in the annexin-V assay. These data imply that Aurora-A kinase inhibition may be linked to apoptosis induction and cell cycle arrest. Furthermore, their higher docking score in the study confirmed evidence of Aurora-kinase suppression. It was observed that fluorine and imidazole increased the H-bond and lipophilic interactions with the binding residue. Also, the substitution of electron-rich and lipophilic groups increased hydrophobic interactions. Moreover, the three-atom linkage (CH2NHCH2) expanded compound 5h to fill the cavity. Based on current findings, it is concluded that compounds 5h and 5e with strong Aurora-A kinase suppression may be promising anticancer agents.

HPLC-PDA Method for Quantification of Bioactive Compounds in Crude Extract and Fractions of Aucklandia costus Falc. and Cytotoxicity Studies against Cancer Cells.

Aucklandia costus Falc. (Synonym: Saussurea costus (Falc.) Lipsch.) is a perennial herb of the family Asteraceae. The dried rhizome is an essential herb in the traditional systems of medicine in India, China and Tibet. The important pharmacological activities reported for Aucklandia costus are anticancer, hepatoprotective, antiulcer, antimicrobial, antiparasitic, antioxidant, anti-inflammatory and anti-fatigue activities. The objective of this study was the isolation and quantification of four marker compounds in the crude extract and different fractions of A. costus and the evaluation of the anticancer activity of the crude extract and its different fractions. The four marker compounds isolated from A. costus include dehydrocostus lactone, costunolide, syringin and 5-hydroxymethyl-2-furaldehyde. These four compounds were used as standard compounds for quantification. The chromatographic data showed good resolution and excellent linearity (r2 ˃ 0.993). The validation parameters, such as inter- and intraday precision (RSD < 1.96%) and analyte recovery (97.52-110.20%; RSD < 2.00%),revealed the high sensitivity and reliability of the developed HPLC method. The compounds dehydrocostus lactone and costunolide were concentrated in the hexane fraction (222.08 and 65.07 µg/mg, respectively) and chloroform fraction (99.02 and 30.21 µg/mg, respectively), while the n-butanol fraction is a rich source of syringin (37.91 µg/mg) and 5-hydroxymethyl-2-furaldehyde (7.94 µg/mg). Further, the SRB assay was performed for the evaluation of anticancer activity using lung, colon, breast and prostate cancer cell lines. The hexane and chloroform fractions show excellent IC50 values of 3.37 ± 0.14 and 7.527 ± 0.18 µg/mL, respectively, against the prostate cancer cell line (PC-3).

Synthesis of novel antioxidant and antitumor 5-aminopyrazole derivatives, 2D/3D QSAR, and molecular docking.

5-Aminopyrazole serves as a vital precursor for several biologically active pyrazoloazines, including pyrazolopyridine, pyrazolopyrimidine, and pyrazolotriazine, as well as Schiff bases, thiourea, and phthalimide derivatives. In this study, we structurally characterized novel pyrazole derivatives by spectral IR, 1H and 13C NMR, and MASS spectroscopy. We also evaluated antioxidant activity of various derivatives using ABTS and DPPH methods and cytotoxicity in the hepatocellular carcinoma Hep-G2 cells by SRB assay. The most potent antitumor molecules were 5-aminopyrazole derivative 3, chloroacetanilide derivative 8, maleimide derivative 10a, pyrazolopyrimidine 16, and enamine 19, with IC50 values of 41, 3.6, 37, 24.4, and 17.7 µM, respectively. Complementary computational studies predicted QSAR and bioactivity of these molecules. Interestingly, the most effective compounds were also predicted to be kinase inhibitors; in addition, molecular docking with liver receptors (3MBG, 4XCU, and 4G9C) predicted promising interactions.

Synergetic Effect of Tumor Treating Fields and Zinc Oxide Nanoparticles on Cell Apoptosis and Genotoxicity of Three Different Human Cancer Cell Lines.

Cancer remains a leading cause of death worldwide, despite extraordinary progress. So, new cancer treatment modalities are needed. Tumor-treating fields (TTFs) use low-intensity, intermediate-frequency alternating electric fields with reported cancer anti-mitotic properties. Moreover, nanomedicine is a promising therapy option for cancer. Numerous cancer types have been treated with nanoparticles, but zinc oxide nanoparticles (ZnO NPs) exhibit biocompatibility. Here, we investigate the activity of TTFs, a sub-lethal dose of ZnO NPs, and their combination on hepatocellular carcinoma (HepG2), the colorectal cancer cell line (HT-29), and breast cancer cell lines (MCF-7). The lethal effect of different ZnO NPs concentrations was assessed by sulforhodamine B sodium salt assay (SRB). The cell death percent was determined by flow cytometer, the genotoxicity was evaluated by comet assay, and the total antioxidant capacity was chemically measured. Our results show that TTFs alone cause cell death of 14, 8, and 17% of HepG2, HT-29, and MCF-7, respectively; 10 µg/mL ZnO NPs was the sub-lethal dose according to SRB results. The combination between TTFs and sub-lethal ZnO NPs increased the cell death to 29, 20, and 33% for HepG2, HT-29, and MCF-7, respectively, without reactive oxygen species increase. Increasing NPs potency using TTFs can be a novel technique in many biomedical applications.

The anti-COVID-19 drug Favipiravir: Degradation, Method development, Validation, NMR/LC-MS characterization, and In-vitro safety evaluation.

It is critical to characterize the degradation products of therapeutic drugs to determine their safety as these degradation products may possess fatal effects on the human physiological system. Favipiravir (FVP), a novel anti-Covid-19 drug, that is recently used all over the world with a great impact on humanity was our target to explore more about its toxicity, the margins of its safety, and its degradants in different degradation conditions. The goal of this study is to identify, characterize, and confirm the structures of FVP oxidative and alkaline breakdown products, as well as to assess their safety utilizing in-vitro SRB cytotoxicity assay on normal human skin fibroblasts (NHSF) cell lines. After oxidative and alkaline degradation of FVP, one degradation product was produced in each condition which was isolated from FVP using flash chromatography, characterized by 1HNMR and LC-MS/MS techniques. A reversed-phase Thermo Fischer Hypersil C18 column (4.6 × 150 mm, 5 m) was used to achieve HPLC chromatographic separation. Acetonitrile-5 mM potassium dihydrogen phosphate (pH 2.5) (50:50, v/v) was employed as the mobile phase, with a flow rate of 1 mL/min. At 332 nm, the column effluent was measured. Over the concentration range of 0.5-100 µg/mL, the calibration curve was linear. The intra-day and inter-day relative standard deviations were less than 2%, and good percentage recoveries were obtained that fulfilled the acceptance criteria of the International Conference on Harmonization (ICH) recommendations. The Plackett-Burman design was used to assess the robustness. Each degradant was isolated single using Flash chromatography and methylene chloride: methanol gradient mobile phase. The chemical structures of the degradation products have been confirmed and compared to the intact FVP using 1H-NMR, and Mass spectroscopy. A postulated mechanism of the degradation process has been depicted and the degradants fragmentation pattern has been portrayed. In addition, the in vitro SRB cytotoxicity assay to evaluate the safety profile of FVP and the degradation end products showed their high safety margin in both conditions with IC50 ˃100 µg/ml with no signs of toxicity upon examination of the treated NHSF cells under the optical microscope.

Synthesis and biological evaluation of novel 2-alkoxycarbonylallylester phosphonium derivatives as potential anticancer agents.

Several phosphonium derivatives have been synthesized from Baylis-Hillman (BH) reaction derived allyl bromides and aryl phosphines as mitochondria targeting anticancer agents. In vitro cell proliferation inhibition studies on various solid tumor cell lines indicate that most of the compounds exhibit IC50 values in µM concentrations. Further studies reveal that ß-substituted BH bromide derived phosphonium derivatives enhance the biological activity to low µM IC50 values. In vitrometabolic studies show that the lead candidate compound 16 inhibits the production of mitochondrial ATP, increases the proton leak within the mitochondrial membrane and abolishes the spare respiratory capacity in a concentration dependent manner.

Molecular Docking Studies and Biological Evaluation of Berberine-Benzothiazole Derivatives as an Anti-Influenza Agent via Blocking of Neuraminidase.

In this study, we have introduced newly synthesized substituted benzothiazole based berberine derivatives that have been analyzed for their in vitro and in silico biological properties. The activity towards various kinds of influenza virus strains by employing the cytopathic effect (CPE) and sulforhodamine B (SRB) assay. Several berberine-benzothiazole derivatives (BBDs), such as BBD1, BBD3, BBD4, BBD5, BBD7, and BBD11, demonstrated interesting anti-influenza virus activity on influenza A viruses (A/PR/8/34, A/Vic/3/75) and influenza B viral (B/Lee/40, and B/Maryland/1/59) strain, respectively. Furthermore, by testing neuraminidase activity (NA) with the neuraminidase assay kit, it was identified that BBD7 has potent neuraminidase activity. The molecular docking analysis further suggests that the BBD1-BBD14 compounds' antiviral activity may be because of interaction with residues of NA, and the same as in oseltamivir.

Structure elucidation {spectroscopic, single crystal X-ray diffraction and computational DFT studies} of new tailored benzenesulfonamide derived Schiff base copper(II) intercalating complexes: Comprehensive biological profile {DNA binding, pBR322 DNA cleavage, Topo I inhibition and cytotoxic activity}.

New tailored copper(II)-based intercalating complexes [Cu(L1)2] (1) and [Cu(L2)2] (2) were synthesized from Schiff base scaffold HL1 and HL2(E)-4-(2-((2-hydroxy-3-methoxybenzylidene)amino)ethyl)benzenesulfonamide and (E)-4-(2-((2-hydroxybenzylidene)amino)ethyl)benzenesulfonamide, respectively. The structure elucidation of complexes 1 and 2 was carried out by employing various spectroscopic techniques viz., FT-IR, UV-vis, ESI-MS, EPR and single X-ray crystal diffraction studies. The complexes 1 and 2 were crystallized in monoclinic P21/n and triclinic P-1 space group, respectively possessing square planar geometry around Cu(II) coordinated with N,O-donor Schiff base ligands. An analysis of Hirshfeld surfaces of complexes 1 and 2 were performed to ascertain different intra and intermolecular non-covalent interactions (H-bonding, CH⋯ πetc.) responsible for the stabilization of crystal lattices. Calculations based on Density functional theory (B3LYP/DFT), have been carried out to obtain energies of Frontier molecular orbitals. Comparative in vitro binding profile of complexes 1 and 2 with ct-DNA was evaluated employing various biophysical techniques viz., UV-vis, fluorescence, circular dichroism and cyclic voltammetry which suggested non-covalent intercalative binding mode with more avid binding propensity of complex 1 compared to complex 2. The cleavage experiments of complex 1 was performed by gel electrophoretic assay which revealed efficient cleavage mediated via oxidative pathway. Furthermore, topoisomerase I enzymatic activity of complex 1 was carried out employing gel electrophoretic assay which demonstrated significant inhibitory effects at a low concentration of 25 µM. The cytotoxic potential of complex 1 was analyzed by SRB assay on a panel of selected human cancer cell lines which revealed selective activity for MCF-7 (breast cancer) cell line with GI50 = 16.21 µg/ml.

Rat cardiomyocyte H9c2(2-1)-based sulforhodamine B assay as a promising in vitro method to assess the biological component of effluent toxicity.

The treatment of wastewaters is crucial to maintain the ecological status of receiving waters, and thereby guarantee the protection of aquatic life and human health. Wastewater quality evaluation is conventionally based on physicochemical parameters, but increasing attention has been paid to integrate physicochemical and biological data. Nevertheless, the regulatory use of fish in biological testing methods has been subject to various ethical and cost concerns, and in vitro cell-based assays have thus become an important topic of interest. Hence, the present study intends: (a) to evaluate the efficiency of two different sample pre-concentration techniques (lyophilisation and solid phase extraction) to assess the toxicity of municipal effluents on rat cardiomyoblast H9c2(2-1) cells, and (b) maximizing the use of the effluent sample collected, to estimate the environmental condition of the receiving environment. The gathered results demonstrate that the H9c2(2-1) sulforhodamine B-based assay is an appropriate in vitro method to assess biological effluent toxicity, and the best results were attained by lyophilising the sample as pre-treatment. Due to its response, the H9c2(2-1) cell line might be a possible alternative in vitro model for fish lethal testing to assess the toxicity of municipal effluents. The physicochemical status of the sample suggests a high potential for eutrophication, and iron exceeded the permissible level for wastewater discharge, possibly due to the addition of ferric chloride for wastewater treatment. In general, the levels of carbamazepine and sulfamethoxazole are higher than those reported for other countries, and both surpassed the aquatic protective values for long-term exposure.

Design, Synthesis, and Cytotoxic Activity of 3-Aryl-N-hydroxy-2-(sulfonamido)propanamides in HepG2, HT-1080, KB, and MCF-7 Cells.

A new series of (sulfonamido)propanamides (6a1-6a13, 6b1-6b15, 7c1-7c5, 6d1-6d5, 6e1-6e6) was designed and synthesized. All the synthesized compounds were characterized by NMR and mass spectrometry. The target compounds were evaluated for their in vitro cytotoxic activity against hepatocellular carcinoma (HepG2), fibrosarcoma (HT-1080), mouth epidermal carcinoma (KB), and breast adenocarcinoma (MCF-7) cell lines with the sulforhodamine B (SRB) assay, with gemcitabine and mitomycin C as positive controls. Most of these compounds exhibit a more potent cytotoxic effect than the positive control group on various cancer cell lines and the most potent compound, 6a7, shows the IC50 values of 29.78±0.516 µm, 30.70±0.61 µm, and 64.89±3.09 µm in HepG2, HT-1080, KB, and MCF-7 cell lines, respectively. Thus, these compounds with potent cytotoxic activity have potential for development as new chemotherapy agents.

Biological evaluation and pharmacophore modeling of some benzoxazoles and their possible metabolites.

A series of benzoxazole derivatives and some possible primary metabolites were evaluated as anticancer agents. In vitro anti-proliferative activities of the compounds were tested using the SRB assay on cancerous (HeLa) and non-cancerous (L929) cell lines. It was found that 17 of 21 tested compounds had cytotoxic activity on HeLa cells and the cytotoxic activities of the compounds were 15-700 times higher than on L929 cells. We generated two distinct pharmacophore models for the cytotoxic activities of the compounds on HeLa and L929 cells. While active compounds such as camptothecin and X8 fitted the two models generated for both cell lines, selective cytotoxic compounds such as XT3B fitted only the model generated for HeLa cells. Evaluation of the genotoxic activities of the cytotoxic compounds with the alkaline comet assay revealed that compounds X17 and XT3 showed strong genotoxic effects against HeLa cells at low concentrations whereas they had no genotoxic effect on L929 cells. Due to the selective ability for inducing DNA strand breaks only on cancerous cells, the compounds were identified as effective derivatives for anticancer candidates.

Characterization of chickpea (Cicer arietinum L.) lectin for biological activity.

Lectins are proteins that are subject of intense investigations. Information on lectin from chickpea (Cicer arietinum L.) with respect to its biological activities are very limited. In this study, we purified lectin from the seeds of chickpea employing DEAE-cellulose and SP-Sephadex ion exchange chromatography and identified its molecular subunit mass as 35 kDa. The free radical scavenging activity of lectin measured by the DPPH assay has IC50 of 0.88 µg/mL. Lectin exerted antifungal activity against Candida krusei, Fusarium oxysporium oxysporium, Saccharomyces cerevisiae and Candida albicans, while antibacterial activity against E. coli, B. subtilis, S. marcescens and P. aeruginosa. The minimum inhibitory concentrations were 200, 240, 160 and 140 µg for C. krusei, F. oxysporium, S. cerevisiae and C. albicans respectively. Lectin was further examined for its antiproliferative potential against cancerous cell line. The cell viability assay indicated a high inhibition activity on Ishikawa, HepG2, MCF-7 and MDA-MB-231 with IC50 value of 46.67, 44.20, 53.58 and 37.46 µg/mL respectively. These results can provide a background for future research into the benefits of chickpea lectin to pharmacological perspective.

Natural abenquines and synthetic analogues: Preliminary exploration of their cytotoxic activity.

In this study, we explore the cytotoxic activity of four natural abenquines (2a-d) and fourteen synthetic analogues (2e-j and 3a-h) against a panel of six human cancer cell lines using a SRB assay. It was found that most of the compounds revealed higher levels of cytotoxic activities than naturally occurring abenquines. The analogues carrying ethylpyrrolidinyl and ethylpyrimidinyl with either an acetyl group (2h-i) or a benzoyl group (3f-g), were the most potent against all human cancer cell lines and displayed EC50 between a range of 0.6-3.4µM. Notably, of the compounds tested, compound 2i proved the most cytotoxic against both ovarian (A2780) and breast (MCF7) cells, showing EC50=0.6 and 0.8µM respectively. Likewise, the analogues 2i, 3f and 3g showed strong activity against cell HT29 with EC50=0.9µM for these compounds.

Assessment of free radical scavenging and anti-proliferative activities of Tinospora cordifolia Miers (Willd).

BACKGROUND: Tinospora cordifolia (Guduchi or Amrita) is an important drug of Ayurvedic System of Medicine and found mention in various classical texts for the treatment of diseases such as jaundice, fever, diabetes, cancer and skin disease etc. In view of its traditional claims, antioxidant and anti-proliferative activities were evaluated in the present study. METHODS: Ethanol extract (TCE) and subsequent petroleum ether (TCP), dichloromethane (TCD), n-Butanol (TCB) and aqueous (TCA) fractions of were prepared from stems of T cordifolia. Total phenolic, flavonoid content and anti-oxidant activity was assessed by different methods. Anti-proliferative activity was assessed in cervical carcinoma (HeLa) cell lines by MTT and SRB assay. RESULTS: Ethanol extract and n-butanol fractions shown to be superior in their scavenging activity in all the tested methods. n-butanol fractions shown antioxidant activity with an IC50 of 14.81 ± 0.53, 29.48 ± 2.23, 58.20 ± 0.70 and 21.17 ± 1.19 µg/mL by DPPH, ABTS, Nitric oxide and iron chelating activities respectively. Anti-proliferative activity results demonstrates that the TCD and ethanol extract of T cordifolia exhibits potent cytotoxic effect against HeLa with an IC50 of 54.23 ± 0.94 µg/mL and 101.26 ± 1.42 µg/mL respectively by MTT assay; and with an IC50 of 48.91 ± 0.33 µg/mL and 87.93 ± 0.85 µg/mL respectively by SRB assay. CONCLUSION: The outcomes of the present study support the fact that T Cordifolia is a promising source of antioxidant agent and propose its further investigation. Moreover, dichloromethane fraction of T cordifolia shown to be the most potent anti-proliferative fraction and further mechanistic and phytochemical investigations are under way to identify the active principles.

Targeting cancer cells with oleanolic and ursolic acid derived hydroxamates.

Oleanolic and ursolic acid derived hydroxamates were easily obtained from their parent compounds; they were screened for their cytotoxicity applying SRB assays employing several human tumor cell lines. Low EC50 values were determined for compounds in which the nitrogen as well as the oxygen in the hydroxamic acid part still holds acidic hydrogens. Thus, ursolic acid derived compounds having at least an OH and/or NH moiety in the hydroxamate part of the molecule showed good cytotoxicity but they are significantly less selective for the tumor cells than oleanolic acid derived compounds. Good results were determined for oleanolic acid derived 7 for tumor cell lines 518A2 (melanoma, EC50=3.3 µM), A2780 (ovarian carcinoma, EC50=3.4 µM) and HT29 (colon adenocarcinoma, EC50=5.6 µM) while being significantly less cytotoxic for fibroblasts (EC50=20.4 µM).

Chrysin-benzothiazole conjugates as antioxidant and anticancer agents.

7-(4-Bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one, obtained from chrysin with 1,4-dibromobutane, was combined with a wide range of 6-substituted 2-aminobenzthiazoles, which had been prepared from the corresponding anilines with potassium thiocyanate. Free radical scavenging efficacies of newer analogues were measured using DPPH and ABTS assays, in addition to the assessment of their anticancer activity against cervical cancer cell lines (HeLa and CaSki) and ovarian cancer cell line (SK-OV-3) implementing the SRB assay. Cytotoxicity of titled compounds was checked using Madin-Darby canine kidney (MDCK) non-cancer cell line. Overall, 6a-r indicated remarkable antioxidant power as DPPH and ABTS(+) scavengers; particularly the presence of halogen(s) (6g, 6h, 6j-6l) was favourable with IC50 values comparable to the control ascorbic acid. Unsubstituted benzothiazole ring favored the activity of resultant compounds (6a and 6r) against HeLa cell line, whereas presence of chlorine (6g) or a di-fluoro group (6k) was a key to exert strong action against CaSki. Moreover, a mono-fluoro (6j) and a ketonic functionality (6o) were beneficial to display anticipated anticancer effects against ovarian cancer cell line SK-OV-3. The structural assignments of the new products were done on the basis of IR, (1)H NMR, (13)C NMR spectroscopy and elemental analysis.

Chemoenzymatic synthesis and cytotoxicity of oenanthotoxin and analogues.

We developed a synthetic scheme for the synthesis of naturally occurring (14R)-oenanthotoxin and several analogs. Key-steps of this synthesis were an efficient homo-coupling of alkynes and a chemoenzymatic resolution of racemic oenanthotoxin using novozyme 435 and vinyl acetate. The compounds were screened for their cytotoxic activity using a photometric sulforhodamine B assays and several human tumor cell lines. Oenanthotoxin and many derivatives thereof were cytotoxic to tumor cell lines as well as to non-malignant mouse fibroblasts. The highest activity was determined for human ovarian cancer cells A2780 with EC50 = 3.8 µM.

Simple structural modifications confer cytotoxicity to allobetulin.

A variety of allobetulin derivatives was synthesized from allobetulin or allobetulone. These compounds were screened for their cytotoxic activity using a photometric SRB assay employing six different human tumor cell lines. In summary, opening of ring A of allobetulin in general lowers the cytotoxicity, but the 2,3-seco diethyl ester was highly cytotoxic and remarkable selective for A549 lung carcinoma cells while being significantly less cytotoxic for non-malignant mouse fibroblasts. The introduction of an amino group at position C-3 in the allobetulin skeleton enhances cytotoxicity and furnishes highly cytotoxic compounds. Their selectivity to distinguish between cancer cell and non-malignant cell depends on the configuration at position C-3.

Mannosylated solid lipid nanoparticles for lung-targeted delivery of Paclitaxel.

OBJECTIVE: The present study discusses paclitaxel (PTX)-loaded mannosylated-DSPE (Distearoyl-phosphatidyl-ethanolamine) solid lipid nanoparticles (M-SLNs) using mannose as a lectin receptor ligand conjugate for lung cancer targeting and to increase the anticancer activity of PTX against A549 lung's epithelial cancer cells. MATERIALS AND METHODS: The PTX-SLNs were prepared by solvent injection method and mannose was conjugated to the free amine group of stearylamine. The M-SLNs obtained were characterized for their particle size, polydispersity index, zeta potential and morphology by transmission electron microscope. RESULTS: The M-SLNs were spherical in shape with 254 ± 2.3 nm average size, positive zeta potential (3.27 mV), 79.4 ± 1.6 drug entrapment efficiency and showed the lower extent of drug release 40% over 48 h in vitro. Cytotoxicity study on A549 cell lines and biodistrubtion study of drug revealed that M-SLNs deliver a higher concentration of PTX as compared to PTX-SLNs in an alveolar cell site. DISCUSSION AND CONCLUSION: These results suggested that mannosylated M-SLNs are safe and potential vector for lung cancer targeting.