Remarkable Regioselective Position-10 Bromination of Bacteriopyropheophorbide-<i>a</i> and Ring-B Reduced Pyropheophorbide-<i>a</i>

Ethirajan, Manivannan,Joshi, Penny,William, White H.,Ohkubo, Kei,Fukuzumi, Shunichi,Pandey, Ravindra K. American Chemical Society 2011 Organic letters Vol.13 No.8

<P>Both bacteriopyropheophorbide-<I>a</I> and ring-B reduced pyropheophorbide-<I>a</I> on reacting with NBS (<I>N</I>-bromosuccinamide) undergo electrophilic bromination to provide 10-bromo analogs. The electronic nature of the substituents present at position-3 did not make any difference in the regioselective outcome of the brominated products. These relatively stable brominated chlorins and bacteriochlorins provide an easy way of introducing a wide variety of functionalities, which could be extremely useful in developing improved agents for biomedical applications and supramolecular chemistry.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/orlef7/2011/orlef7.2011.13.issue-8/ol200314v/production/images/medium/ol-2011-00314v_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ol200314v'>ACS Electronic Supporting Info</A></P>

Cytotoxic and Antibacterial Activities of Gossypin

D. Chamundeeswari,Ethirajan Sukumar,K. Amar,N. Brahmananda Reddy,I. Anil Kumar,B. V. Chowdry,K. Samatha 한국생약학회 2007 Natural Product Sciences Vol.13 No.4

a naturally occurring polyhydroxy flavonoid, when subjected to in vitro cytotoxic screeningagainst vero cell lines exhibited 68.75% inhibition at a concentration of 1000 .g. When tested against fivebacteria and five fungi, the flavone derivative showed a moderate activity against Staphylococcus aureus and, mild inhibition against Pseudomonas aerugenosa and Salmonella typhi and no activity againstany of the tested fungi, in the concentrations studied.KeywordsGossypin, cytotoxicity, antibacterial activity

Synthesis, Photophysical,Electrochemical, Tumor-Imaging,and Phototherapeutic Properties of Purpurinimide-<i>N</i>-substituted Cyanine Dyes Joined with Variable Lengths of Linkers

Williams, MichaelP. A.,Ethirajan, Manivannan,Ohkubo, Kei,Chen, Ping,Pera, Paula,Morgan, Janet,White, William H.,Shibata, Masayuki,Fukuzumi, Shunichi,Kadish, Karl M.,Pandey, Ravindra K. American ChemicalSociety 2011 Bioconjugate chemistry Vol.22 No.11

<P>Purpurinimide methyl esters, bearing variable lengthsof N-substitutions,were conjugated individually to a cyanine dye with a carboxylic acidfunctionality. The results obtained from <I>in vitro</I> and <I>in vivo</I> studies showed a significant impactof the linkers joining the phototherapeutic and fluorescence imagingmoieties. The photosensitizer–fluorophore conjugate with aPEG linker showed the highest uptake in the liver, whereas the conjugatelinked with two carbon units showed excellent tumor-imaging and PDTefficacy at 24 h postinjection. Whole body imaging and biodistributionstudies at variable time points portrayed enhanced fluorescent uptakeof the conjugates in the tumor compared to that in the skin. Interestingly,the conjugate with the shortest linker and the one joining with twocarbon units showed faster clearance from normal organs, e.g., theliver, kidney, spleen, and lung, compared to that in tumors. Bothimaging and PDT efficacy of the conjugates were performed in BALB/cmice bearing Colon26 tumors. Compared to the others, the short linkerconjugate showed poor tumor fluorescent properties and as a corollarydoes not exhibit the dual functionality of the photosensitizer–fluorophoreconjugate. For this reason, it was not evaluated for <I>in vivo</I> PDT efficacy. However, in Colon26 tumor cells (<I>in vitro</I>), the short linker was highly effective. Among the conjugates withvariable linkers, the rate of energy transfer from the purpurinimidemoiety to the cyanine moiety increased with deceasing linker length,as examined by femtosecond laser flash photolysis measurements. Noelectron transfer from the purpurinimide moiety to the singlet excitedstate of the cyanine moiety or from the singlet excited state of thecyanine moiety to the purpurinimide moiety occurred as indicated bya comparison of transient absorption spectra with spectra of the one-electronoxidized and one-electron reduced species of the conjugate obtainedby spectroelectrochemical measurements.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bcches/2011/bcches.2011.22.issue-11/bc200345p/production/images/medium/bc-2011-00345p_0016.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bc200345p'>ACS Electronic Supporting Info</A></P>

Structure-activity relationship of capsaicin analogs and transient receptor potential vanilloid 1-mediated human lung epithelial cell toxicity.

Thomas, Karen C,Ethirajan, Manivannan,Shahrokh, Kiumars,Sun, Hao,Lee, Jeewoo,Cheatham, Thomas E,Yost, Garold S,Reilly, Christopher A Williams Wilkins 2011 The Journal of pharmacology and experimental thera Vol.337 No.2

<P>Activation of intracellular transient receptor potential vanilloid-1 (TRPV1) in human lung cells causes endoplasmic reticulum (ER) stress, increased expression of proapoptotic GADD153 (growth arrest- and DNA damage-inducible transcript 3), and cytotoxicity. However, in cells with low TRPV1 expression, cell death is not inhibited by TRPV1 antagonists, despite preventing GADD153 induction. In this study, chemical variants of the capsaicin analog nonivamide were synthesized and used to probe the relationship between TRPV1 receptor binding, ER calcium release, GADD153 expression, and cell death in TRPV1-overexpressing BEAS-2B, normal BEAS-2B, and primary normal human bronchial epithelial lung cells. Modification of the 3-methoxy-4-hydroxybenzylamide vanilloid ring pharmacophore of nonivamide reduced the potency of the analogs and rendered several analogs mildly inhibitory. Correlation analysis of analog-induced calcium flux, GADD153 induction, and cytotoxicity revealed a direct relationship for all three endpoints in all three lung cell types for nonivamide and N-(3,4-dihydroxybenzyl)nonanamide. However, the N-(3,4-dihydroxybenzyl)nonanamide analog also produced cytotoxicity through redox cycling/reactive oxygen species formation, shown by inhibition of cell death by N-acetylcysteine. Molecular modeling of binding interactions between the analogs and TRPV1 agreed with data for reduced potency of the analogs, and only nonivamide was predicted to form a 'productive' ligand-receptor complex. This study provides vital information on the molecular interactions of capsaicinoids with TRPV1 and substantiates TRPV1-mediated ER stress as a conserved mechanism of lung cell death by prototypical TRPV1 agonists.</P>

Nuclear Anomalies, Chromosomal Aberrations and Proliferation Rates in Cultured Lymphocytes of Head and Neck Cancer Patients

George, Alex,Dey, Rupraj,Bhuria, Vikas,Banerjee, Shouvik,Ethirajan, Sivakumar,Siluvaimuthu, Ashok,Saraswathy, Radha Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.3

Head and neck cancers (HNC) are extremely complex disease types and it is likely that chromosomal instability is involved in the genetic mechanisms of its genesis. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures (72 hours) from 72 study subjects - 36 newly diagnosed HNC squamous cell carcinoma patients and 36 healthy ethnic controls. We estimated chromosome instability (CIN) using chromosomal aberration (CA) analysis and nuclear level anomalies using the Cytokinesis Block Micronucleus Cytome Assay (CBMN Cyt Assay). The proliferation rates in cultures of peripheral blood lymphocytes (PBL) were assessed by calculating the Cytokinesis Block Proliferation Index (CBPI). Our results showed a significantly higher mean level of spontaneous chromosome type aberrations (CSAs), chromatid type aberration (CTAs) dicentric chromosomes (DIC) and chromosome aneuploidy (CANE UP) in patients (CSAs, $0.0294{\pm}0.0038$; CTAs, $0.0925{\pm}0.0060$; DICs, $0.0213{\pm}0.0003$; and CANE UPs, $0.0308{\pm}0.0035$) compared to controls (CSAs, $0.0005{\pm}0.0003$; CTAs, $0.0058{\pm}0.0015$; DICs, $0.0005{\pm}0.0003$; and CANEUPs, $0.0052{\pm}0.0013$) where p<0.001l. Similarly, spontaneous nuclear anomalies showed significantly higher mean level of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) among cases (MNi, $0.01867{\pm}0.00108$; NPBs, $0.0156{\pm}0.00234$; NBUDs, $0.00658{\pm}0.00068$) compared with controls (MNi, $0.00027{\pm}0.00009$; NPBs, $0.00002{\pm}0.00002$; NBUDs, $0.00011{\pm}0.00007$).The evaluation of CBPI supported genomic instability in the peripheral blood lymphocytes showing a significantly lower proliferation rate in HNC patients ($1.525{\pm}0.005552$) compared to healthy subjects ($1.686{\pm}0.009520$) (p<0.0001). In conclusion, our preliminary results showed that visible spontaneous genomic instability and low rate proliferation in the cultured peripheral lymphocytes of solid tumors could be biomarkers to predict malignancy in early stages.