Orientadores: João Ernesto de Carvalho, Mary Ann Foglio / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-18T11:34:15Z (GMT). No. of bitstreams: 1 Rizzo_LarissaYokota_M.pdf: 2545881 bytes, checksum: 63ab51d7b009706ec8505aa2b3ded262 (MD5) Previous issue date: 2011 / Resumo: A pesquisa de drogas anticâncer através da triagem de extratos e princípios ativos obtidos de fontes naturais possibilitou a descoberta e o desenvolvimento de diversos quimioterápicos hoje utilizados no tratamento do câncer. Este projeto teve como objetivo avaliar a atividade anticâncer de Psidium guajava L. (nome popular: goiabeira), espécie eleita através de levantamento etnofarmacológico para atividade antiparasitária. Após a colheita, o material vegetal foi submetido a um processo de extração a quente por Soxhlet, com diclorometano e etanol 95%, originando o extrato bruto diclorometânico (EBD) e etanólico (EBE), respectivamente. O extrato bruto ativo, EBD, foi submetido a diversos fractionamentos biomonitorados, até a obtenção de uma fração enriquecida nos meroterpenos guajadial, psidial A e seus isômeros, princípios ativos da espécie vegetal. Todas as amostras (extratos brutos e frações enriquecidas) tiveram sua potencial atividade anticâncer avaliadas in vitro frente a um painel de dez linhagens tumorais humanas, cedidas pelo National Cancer Institute (NCI, Estados Unidos), a saber: K562 (leucemia), MCF-7 (mama), NCI/ADR-RES (ovário resistente a múltiplas drogas), NCI-H460 (pulmão), UACC62 (melanoma), PC-3 (próstata), HT-29 (cólon), OVCAR-03 (ovário), U251 (glioma) and 786-0 (rim). A fração ativa enriquecida nos meroterpenos foi avaliada in vivo no tumor sólido de Ehrlich, em camundongos Balb/C, reduzindo significativamente o crescimento tumoral. Além da atividade antitumoral observada in vivo, a análise macroscópica do útero indicou aumento em tamanho e peso em relação aos grupos controle negativo (salina) e positivo (doxorrubicina). As moléculas de guajadial e psidial A apresentam propriedades físico-químicas semelhantes ao estradiol e ao tamoxifeno e estudos de docking molecular sugerem que ambos os compostos se liguem no sítio de ligação no receptor de estrógeno (ER), analogamente ao tamoxifeno. A capacidade de reduzir o crescimento tumoral e, ao mesmo tempo, estimular o útero indicam que guajadial e psidial A possivelmente agem como fitoestrógenos, possuindo um mecanismo de ação semelhante ao tamoxifeno, atuando como SERMs (Selective Estrogen Receptor Modulators) e agindo como agonistas e antagonistas de forma tecido específica / Abstract: Anticancer drug research based on screening of natural sources enabled the discovery of several drugs that are used in cancer treatment. This project aimed to evaluate the in vitro and in vivo anticancer activity of Psidium guajava L. (popular name: guava), elected for its ethnopharmacological use for antiparasitic activity. After harvesting, the vegetal material was extracted in Soxhlet with dicloromethane and then ethanol 95%, leading to the dicloromethane crude extract (DCE) and the ethanolic crude extract (ECE), respectively.The active extract, DCE, was submitted to several biomonitored fractionating processes and an active mixture of meroterpenes identified guajadial, psidial A and its isomers as active principles. All samples (crude extract and enriched fractions) were evaluated in vitro for cytotoxic activity against ten human cancer lines (donated by National Cancer Institute, USA): K562 (leukemia), MCF-7 (breast), NCI/ADR-RES (resistant ovarian cancer), NCI-H460 (lung), UACC62 (melanoma), PC-3 (prostate), HT-29 (colon), OVCAR-03 (ovary), U251 (glioma) and 786-0 (kidney). Meroterpenes enriched fraction was evaluated in vivo in the Solid Ehrlich Tumor, in Balb/C mice, and significantly reduced tumor growth. Besides antitumoral activity, macroscopic analysis of uterus showed increased size and weight in comparison to both negative (vehicle) and positive (doxorubicin) control groups. The molecules of guajadial and psidial A display similar physicochemical properties to estradiol and tamoxifen and in silico molecular docking studies suggest that both molecules bind to the estrogen-binding site of ERs analogously to tamoxifen. The ability to reduce breast cancer tumor growth and stimulate the uterus suggests that guajadial and psidial A may act as phytoestrogens, giving insights for a mechanism of action similar to tamoxifen, acting as SERMs (Selective Estrogen Receptor Modulators), having both agonist and antagonist tissue-specific activities / Mestrado / Histologia / Mestre em Biologia Celular e Estrutural

Thesis (M. Sc. (Biochemistry)) -- University of Limpopo, 2021 / Plant-derived products have been used for years in the treatment of various ailments with low or no side effects. Thus, screening of medicinal plants for potential anticancer activity, in vitro, could help identify plant extracts or compounds that can be developed for use as anticancer agents with less or no side effects. The aim of this study was to investigate the probable anticancer effects and induced mechanism of action of Momordica balsamina crude leaf acetone extract in lung A549 cancer cells. The effect of the extract on cell viability, proliferation and cell division cycle were determined using Muse count & viability, Ki67 proliferation and cell cycle assay kits, respectively. The presence of biochemical and morphological features associated with apoptosis were analysed by Muse annexin-V & dead cell assay kit and Acridine orange/Ethidium bromide dual staining. The effect of the extract on the mRNA expression levels of cell cycle regulatory genes was determined using RT PCR. Proteome profiler antibody array was used to determine the effect of the extract on the protein expression levels of apoptosis regulatory genes. The findings revealed that the crude leaf acetone extract of M. balsamina decreased the percentage viability of lung A549 cells with less effect on the percentage viability of normal cells (KMST-6). Furthermore, a significant anti-proliferative effect in extract treated A549 cells was observed. Characteristic nuclear and morphological features of apoptosis such as chromatin and nuclear condensation, externalisation of phosphatidylserine and loss of cell membrane function were observed in A549 cells treated with the extract. Although there was no relative upregulation of Bax and Bad protein expression, a downregulation of the Bcl-xl and Bcl-2 protein expression was observed in extract-treated cells. This led to the release of Cytochrome c and HTRA2/Omi leading to pro-caspase-3 cleavage. Furthermore, presence of HTRA2/Omi in the cytosol inhibited the functions of IAPs such as XIAP and cIAP1/2. Phosphorylation of p53 at different serine residues led to upregulated protein expression levels of p27/Kip1 protein which resulted in the cell division cycle arrest at G0/G1-phase. Reverse transcriptase polymerase chain reaction results showed that the extract modulated mRNA expression levels of p53, p21, cyclin B and cdc2 genes. In summary, M. balsamina extract induced cell division cycle arrest and apoptosis in A549 cells through intrinsic apoptosis pathway via p53-mediated mechanism. / South African Medical Research Council (SAMRC)

Development of Non-Traditional Platinum Anticancer Agents: trans-Platinum Planar Amine Compounds and Polynuclear Platinum Compounds By Daniel E. Lee, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2015 Major Director: Nicholas P Farrell, Ph.D., Professor, Department of Chemistry Platinum anticancer compounds with cis geometry, similar to cisplatin, have been explored to circumvent the cisplatin resistance; however, they were not considered broadly active in cisplatin cells due to exhibiting similar or same cell death mechanism as cisplatin. Platinum compounds with trans geometry were less studied due to transplatin being clinically inactive; but with few structural modifications, they resulted in unaffected cytotoxic activities in cisplatin resistant cells with structural modification by exhibiting different modes of DNA binding. This research focused on further exploring and establishing structure-activity relationship of two promising non-classical series of platinum compounds with trans-geometry: trans-platinum planar amine (TPA) compounds and noncovalently binding polynuclear platinum compounds (PPC-NC). During this research, further optimizations of the reactivity of TPA compounds were accomplished by modifying the leaving carboxylate groups. The effects of modified reactivity were probed by a systematic combination of chemical and biophysical assays, followed by evaluating their biological effects in cells. To establish the structural-activity relationship of PPC-NCs, Mono-, Di-, Tri-, and Tetraplatin NC with charge of 4+, 6+, 8+, and 10+ were synthesized and evaluated by utilizing biophysical and biological assays. Lastly, a new class of polynuclear platinum compounds, Hybrid-PPCs, were synthesized and evaluated to overcome the pharmacokinetic problems of BBR3464, phase II clinical trial anticancer drug developed previously in our laboratory.

Le laboratoire a récemment identifié la protéine Damaged-DNA-Binding 2 (DDB2), connue à l’origine pour son rôle dans la réparation de l’ADN comme une protéine impliquée dans la tumorigenèse mammaire. En effet, nous avons montré son rôle dans la croissance et la progression des tumeurs mammaires via la régulation transcriptionnelle de gènes cibles. Dans ce travail, nous avons montré que la surexpression de DDB2 augmente la sensibilité des cellules tumorales MDA-MB231 et SKBr3 traitées à la doxorubicine et au 5-fluorouracile (5-FU). Inversement, l’inhibition de l’expression de DDB2 dans les cellules T47D qui l’expriment naturellement s’accompagne d’une baisse de la sensibilité à ces agents anticancéreux. Nos résultats montrent que la sensibilité des cellules au 5-FU mais pas à la doxorubicine, lorsque DDB2 est surexprimée, dépend en partie du contrôle négatif qu’exerce cette dernière sur l’activité de NF-κB, en régulant positivement l’expression d’IκBα. Enfin, la recherche d’autres gènes cibles de DDB2, impliqués dans l’apoptose, nous a conduits à celui codant le facteur anti-apoptotique Bcl-2. DDB2 agit négativement sur l’expression de Bcl-2 en interagissant avec une région de l’ADN localisée dans le promoteur P2 du gène correspondant. De part, son rôle anti-apoptotique, la régulation de son expression pourrait bien être à l’origine de la sensibilité aux agents anticancéreux induite par DDB2. L’ensemble de ces résultats met donc en évidence l’intérêt clinique de DDB2 comme marqueur prédictif de la réponse aux agents anticancéreux, et devrait contribuer à une meilleure compréhension des mécanismes impliqués dans l’échappement des cellules tumorales aux thérapies / The laboratory has recently identified the Damaged-DNA Binding 2 protein (DDB2), a protein involved in DNA repair, as an important actor in breast tumorigenesis. Our laboratory has shown that DDB2 is involved in breast tumor growth and progression through the transcriptional regulation of target genes. Thus, the first aim of this work was to study the role of DDB2 and its target genes in the response of breast cancer cells to anticancer drugs. We showed that DDB2 overexpressed in breast cancer cell lines, such as MDA-MB231 and SKBr3, increased the cells sensitivity to apoptosis induced by doxorubicin and 5-Fluorouracil (5-FU). Conversely, the inhibition of DDB2 expression in T47D cells, which express endogenously this protein, decreased cell sensitivity to anticancer agents. Our results showed that cell sensitivity induced by DDB2 expression to 5-FU but not doxorubicin depended on its ability to repress NF-κB activity via the regulation of IκBα expression. At last, the search of potential DDB2 target genes implicated in apoptosis has led us to identify the anti-apoptotic factor Bcl-2. We showed the ability of DDB2 to downregulate Bcl-2 expression via its interaction with DNA region located in P2 promoter of the corresponding gene. Results suggest that Bcl-2 dowregulation by DDB2 could be a major event that explains the enhanced sensitivity of cancer cells to therapeutic agents. Altogether, these data highlight the clinical interest of DDB2, as a predictive marker of the response to anticancer agents. A better understanding of its mode of action will contribute to improve therapeutic treatments and avoid their failure in resistant patients

This work focuses on the design and synthesis of Au(I) and Ag(I) complexes from ligand systems that aim to combine both N-heterocyclic carbene (NHC) and phosphine ligand types. A number of synthetic approaches towards both the ligands and the prepared metal complexes have been developed, with a concerted effort on achieving the desired Au(I) or Ag(I) complexes with minimal reaction steps and synthetic style. The thesis body is divided into two main sections. The first section addresses the preparation of suitable ligand precursors of potential Au(I) and Ag(I) complexes in the form of halo- and phosphino-functionalised imidazolium salts. Several series of haloalkylimidazolium salts were prepared that encompass a range of halogens (Cl, Br, I), alkyl substituents (Me, i-Pr, t-Bu, n-Bu), differing alkyl linker length (n = 0-3), and a variety of organic spacers employed to bridge multi-imidazolium moieties. Novel bidentate and multidentate phosphinoalkylimidazolium salts were synthesised from the various haloalkylimidazolium salts, via the substitution of a halide with nucleophilic diphenylphosphide. A new approach towards rare methylene bridged phosphinomethylimidazolium salts was achieved from the reactions of halomethylimidazolium salts with diphenylphosphine. The second section investigates the preparation of Au(I) and Ag(I) complexes from the halo- and phosphino-functionalised imidazolium salts. A series of dicationic 10, 12, and 14-membered metallacyclic Ag(I) complexes were prepared from the bidentate phosphinoalkylimidazolium salts. The dinuclear Ag(I) metallacycles combine two phosphino-functionalised NHC ligands that are bridged by two coordinated Ag(I) ions in an exclusively head-to-head arrangement. A dinuclear Ag(I) metallacycle was investigated for transmetallation potential to a Au(I) complex and found to selectively transmetallate at the Ag(I) coordinated to the NHC ligands to form a bimetallic metallacycle. Unexpected phosphine oxidation of a 10-membered dinuclear Ag(I) metallacycle resulted in complex disproportionation to an isolable and rare silver(I) trimer. Metal-NHC complexes from haloalkylimidazolium salts have not been reported previously, a novel approach to the synthesis of a series of Au(I) complexes from haloalkylimidazolium salts and a respective gold source was developed and is reported herein. Different synthetic approaches towards Au(I) complexes with the phosphinoalkylimidazolium salts explored a variety of ways to generate the NHC from an imidazolium in the presence of the phosphine. A one-pot, high yielding synthesis of a dinuclear Au(I) complex from PPh3 was also devised, with controlled assembly of the complex resulting in a similar head-to-head ligand arrangement to the dinuclear Ag(I) metallacycles. As an aside, a family of mononuclear [Au(R2NHC)2]+ complexes (R = Me, i-Pr, t- Bu, n-Bu, Cy) prepared previously in our research group, was expanded because of the promising antimitochondrial activity shown by [Au(i-Pr2NHC)2]+. Two new [Au(R2NHC)2]+ complexes with simple alkyl chain functionality were prepared with fine-tuned lipophilicity in close proximity to that of [Au(i-Pr2NHC)2]+.

La cycloaddition 1,3-dipolaire catalysée par le cuivre(I) entre un azoture et un alcyne (CuAAC), réaction de « chimie click » par excellence, suscite un grand intérêt en raison de son efficacité et de sa versatilité. L'objectif premier de cette thèse est d'appliquer cette réaction pour l'élaboration de structures 1,2,3-triazoles fonctionnalisées, en vue d'obtenir des ligands jouant le rôle de « pince à platine ». Les complexes de platine biologiquement actifs rapportés sont de type mono- ou bi-nucléaire et comportent un ou deux cycles triazole. Les complexes obtenus ont fait l'objet d'une étude in vitro d'interaction avec des nucléosides et de l'ADN soit sous forme d'hairpin (épingle à cheveux) soit sous forme plasmidique. Nos complexes ont montrés une réactivité similaire à celle du cisplatine, qui est la métallodrogue de référence. En parallèle, nous présentons les propriétés catalytiques et biologiques de complexes cuivre(I)-NHC (Carbène N-Hétérocyclique), dérivés du [CuCl(SIMes)], mis au point par Nolan et al. Dans un premier temps, un criblage d'activités catalytiques a été réalisé avec divers additifs aromatiques azotés afin d'améliorer l'efficacité de la CuAAC. Dans un deuxième temps, la cytotoxicité et l'activité antitumorale du complexe [CuCl(SIMes)] ont été considérées sur plusieurs lignées cellulaires. Nous rapportons ici, le premier exemple de cuivre(I)-NHC biologiquement actif, présentant une activité largement supérieure à celle du cisplatine. Enfin, la réactivité de ce complexe avec de l‟ADN plasmidique a été évaluée in vitro et nous rapportons sa capacité à couper l‟ADN. / The copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC), a “click chemistry” reaction, is of a great interest thanks to its efficiency and versatility. The present work aims to use this reaction for the elaboration of new functionalised 1,2,3-triazole, as “pincer ligand” to platinum. We have synthesized mono- or binuclear platinum anticancer complexes that contain one or two triazole cycles. These complexes were subject to in vitro tests, in order to investigate the interactions they can establish with both nucleosides and DNA. The results reveal a reactivity similar to cisplatin, the reference metallodrug. In parallel, we present the catalytic and biological properties of copper(I)-NHC complexes, like [CuCl(SIMes)] developed by Nolan et al. At first, a screening of the catalytic activity was realized with diverse nitrogen aromatics additives in order to improve the CuAAC efficiency. Secondly, the cytotoxicity and antitumoral activity of [CuCl(SIMes)] were considered on various cancer cell lines. We report here, the first example of a biologically active copper(I)-NHC, this complexe exhibiting a superior activity than cisplatin. Finally, the reactivity of this copper(I)-NHC with DNA was evaluated in vitro and highlights its capacity to cleave DNA.

Introdução: O carcinoma de células renais metastático (CCRm) é um tumor altamente agressivo e resistente. Seu tratamento é baseado em terapia alvo molecular e citocinas. Avaliamos os efeitos antineoplásicos do Amblyomin-X, sobre CCR. Métodos: Avaliadas culturas de CCR RENCA e fibroblastos normais NIH/3T3 tratadas ou não com Amblyomin-X. Realizados ensaios de viabilidade celular por MTT e determinação, por citometria de fluxo, da proporção de células em apoptose/necrose; expressão da P-gp; Bad; Bax; Bcl-2; ciclina D1; caspase 3; Ki-67; p53; VEGFR1; citocromo c; análise das fase do ciclo celular; e atividade do proteassoma. Analisamos as populações celulares por microscopia eletrônica de varredura. Empregados testes T e One-way ANOVA para análise estatística. Resultados: O Amblyomin-X demonstrou citotoxicidade em células RENCA por indução de apoptose, diminuição de proliferação celular, inibição do proteassoma e modulação do ciclo celular em G0/G1. Em fibroblastos normais não houve citotoxicidade Conclusão: O Amblyomin-X apresentou efeito antineoplásico em CCR e não exerceu efeito citotóxico em células normais, demonstrando um possível potencial terapêutico no tratamento do CCRm. Estudos futuros deverão confirmar estes resultados. / Introduction: Metastatic renal cell carcinoma (mRCC) is a highly agressive and resistant tumour. Its treatment is based on targeted therapies and cytokines. We have evaluated the antineoplasic effects of Amblyomin-X on RCC. Methods: RCC (RENCA) and fibroblasts (NIH/3T3) cell cultures treated or not with Amblyomin-X were evaluated. MTT assay was performed to determine cell viability. Apoptosis/necrosis ratio; expression of P-gp; Bad; Bax; Bcl-2; cyclin D1; caspase-3; Ki-67; p53; VEGFR1; cytochrome c; cell cycle analysis and proteasome activity were obtained by flow cytometry. Cellular populations were analised by Scanning Electron Microscopy. Statistical analyses was performed using T-Tests and One-way ANOVA. Results: Amblyomin-X showed cytotoxic activity on RENCA tumor cells. It has induced apoptosis, decreased tumor cell proliferation, targeted the ubiquitinproteasome system and modulated genes related to cell cycle in G0/G1. There was no toxicity on fibroblasts. Conclusion: Amblyomin-X showed antineoplasic effects on RCC cells preserved normal fibroblast cells. There is a potential role of its therapeutic use in mRCC treatment. Future studies should confirm our initial results.

As part of an International Cooperative Biodiversity Group (ICBG), extracts of plants from Suriname and Madagascar were bioassayed for cytotoxicity and antimalarial activity. Six cytotoxic extracts and one potential antimalarial were selected for fractionation, and yielded a number of bioactive compounds which were characterized by spectroscopy methods. Craspidospermum verticillatum (Apocynaceae) yielded four known indole alkoids. Casimirella sp (Icacinaceae) gave three new and five known diterpenoids. Pentopetia androsaemifolia (Apocynaceae) afforded one new and three known cardenolide glycosides. Physalis angulata (Solanaceae) yielded seven known physalins. Roupellina boivinnii (Apocynaceae) yielded four known and three new cardenolide glycosides, and three known cucurbitacins were isolated from Octolepis aff. dioica (Thymelaeaceae). In addition to these structural studies, a synthetic approach to lucilactaene, a cell cycle inhibitor was developed. / Ph. D.

Yes / Despite significant preclinical promise as anticancer agents, vascular-disrupting agents have yet to fulfil their clinical potential due to systemic toxicities. ICT2588 is a tumour-selective MT1-MMP-targeted prodrug of azademethylcolchicine, ICT2552. We investigate activation of ICT2588 and subsequent release of ICT2552 in tumour cells, and examine its ability to induce G2/M cell cycle arrest. We also explore synergism between ICT2588 and ATR inhibition, since colchicine, in addition to its vascular-disrupting properties, is known to induce G2/M arrest, DNA damage, and trigger apoptosis. Several ATR inhibitors are currently undergoing clinical evaluation. The cellular activation of ICT2588 was observed to correlate with MT1-MMP expression, with selective release of ICT2552 not compromised by cellular uptake and prodrug activation mechanisms. ICT2588 induced G2/M arrest, and triggered apoptosis in MT1-MMP-expressing cells, but not in cells lacking MT1-MMP expression, while ICT2552 itself induced G2/M arrest and triggered apoptosis in both cell lines. Interestingly, we uncovered that the intracellular release and accumulation dynamics of ICT2552 subsequent to prodrug activation provided synergism with an ATR inhibitor in a way not observed with direct administration of ICT2552. These findings have important potential implications for clinical combinations of ICT2588 and DNA repair inhibitors.

The present thesis deals with different aspects of the chemistry of oxovanadium(IV) complexes, their interaction with double stranded DNA, photo-induced DNA cleavage, photo-enhanced cytotoxicity in visible light and red light and localisation and cellular uptake to understand the mechanism of cell death. Chapter I presents a general introduction on potential of transition metal complexes as photochemotherapeutic agents. A brief introduction about Photodynamic Therapy (PDT) as a new alternative to chemotherapy for treating cancer has been made. Various modes of interaction of small molecules with duplex DNA are described. Recent reports on metal-based photocytotoxicity, photo-induced DNA cleavage activity and cellular localization are presented in detail. Objective of the present investigation is also dealt in this Chapter. Chapter II of the thesis deals with the synthesis, characterization, DNA binding and photo-induced DNA cleavage activity of ternary oxovanadium(IV) complexes of ONO-donor 2-(2-hydroxybenzylideneamino)phenol (salamp) and phenanthroline bases to explore the photo-induced DNA cleavage activity in UV-A light of 365 nm and photocytotoxicity in visible light. Chapter III deals with the photo-induced DNA cleavage and photocytotoxicity of ternary oxovanadium(IV) complexes containing ONN-donor N-2-pyridylmethylidine-2-hydroxyphenylamine (Hpyamp) Schiff bases and phenanthroline bases. The objective of this work is to investigate the photo-induced DNA cleavage activity in near-IR light. Photocytotoxicity and cell cycle arrest have been studied in HeLa cancer cells. Chapter IV deals serendipitous discovery of planar triazinuim cationic species by vanadyl-assisted novel ring cyclization reaction. The compounds are synthesised, characterized and their DNA binding and anaerobic photoinduced DNA cleavage activity are presented. The importance of the thiazole moiety in the triazinuim species in cellular uptake has been investigated. Photocytotoxicity, localization and cell death mechanism have been studied in HeLa and MCF-7 cells. Chapter V describes the synthesis, characterization, DNA binding, photo-induced DNA cleavage activity and photocytotoxicity of oxovanadium(IV) complexes containing 2-(1H-benzimidazol-2-yl)-N-(pyridin-2-ylmethylene)ethaneamine (Hpy-aebmz) and curcumin as photosensitizer. The effect of conjugating naphthalimide on Hpy-aebmz on photoinduced DNA cleavage and photocytotoxicity has been studied. Cellular uptake, localization and mechanism of cell death induced by complexes have been investigated. Chapter VI presents ternary oxovanadium(IV) complexes having, 2-((1H-benzimidazol-2-yl)methylimino-methyl)phenol (Hsal-ambmz) and phenanthroline bases. The complexes were synthesized, characterized and their DNA binding property studied. Photo-induced DNA cleavage activity and photocytotoxicity in red light has been discussed. Anthracene has been conjugated to a tridentate ligand to investigate cellular uptake, localization and cell death mechanism. Mitochondria targeting property of the complexes having dipeptide has been studied and compared with clinically used drug Photofrin®. The references have been compiled at the end of each chapter and indicated as superscript numbers in the text. The complexes presented in this thesis are represented by bold-faced numbers. Crystallographic data of the complexes, characterized structurally by single crystal X-ray crystallography, are given in CIF format in the enclosed CD (Appendix-I). Due acknowledgements have been made wherever the work described is based on the findings of other investigators. Any unintentional omission that might have happened due to oversight or mistake is regretted.