Effects of Ferrocene and Ferrocenium on MCF-7 Breast Cancer Cells and Interconnection with Regulated Cell Death Pathways.

The effects of ferrocene (Fc) and ferrocenium (Fc+) induced in triple negative human breast cancer MCF-7 cells were explored by immunofluorescence, flow cytometry, and transmission electron microscopy analysis. The different abilities of Fc and Fc+ to produce reactive oxygen species and induce oxidative stress were clearly observed by activating apoptosis and morphological changes after treatment, but also after tests performed on the model organism D. discoideum, particularly in the case of Fc+. The induction of ferroptosis, an iron-dependent form of regulated cell death driven by an overload of lipid peroxides in cellular membranes, occurred after 2 h of treatment with Fc+ but not Fc. However, the more stable Fc showed its effects by activating necroptosis after a longer-lasting treatment. The differences observed in terms of cell death mechanisms and timing may be due to rapid interconversion between the two oxidative forms of internalized iron species (from Fe2+ to Fe3+ and vice versa). Potential limitations include the fact that iron metabolism and mitophagy have not been investigated. However, the ability of both Fc and Fc+ to trigger different and interregulated types of cell death makes them suitable to potentially overcome the shortcomings of traditional apoptosis-mediated anticancer therapies.

Microwave-Assisted Synthesis: Can Transition Metal Complexes Take Advantage of This "Green" Method?

Microwave-assisted synthesis is considered environmental-friendly and, therefore, in agreement with the principles of green chemistry. This form of energy has been employed extensively and successfully in organic synthesis also in the case of metal-catalyzed synthetic procedures. However, it has been less widely exploited in the synthesis of metal complexes. As microwave irradiation has been proving its utility as both a time-saving procedure and an alternative way to carry on tricky transformations, its use can help inorganic chemists, too. This review focuses on the use of microwave irradiation in the preparation of transition metal complexes and organometallic compounds and also includes new, unpublished results. The syntheses of the compounds are described following the group of the periodic table to which the contained metal belongs. A general overview of the results from over 150 papers points out that microwaves can be a useful synthetic tool for inorganic chemists, reducing dramatically the reaction times with respect to traditional heating. This is often accompanied by a more limited risk of decomposition of reagents or products by an increase in yield, purity, and (sometimes) selectivity. In any case, thermal control is operative, whereas nonthermal or specific microwave effects seem to be absent.

A Comparative Study of the Effects of Platinum (II) Complexes on ß-Amyloid Aggregation: Potential Neurodrug Applications.

Herein the effects of three platinum complexes, namely (SP-4-2)-(2,2'-bipyridine)dichloridoplatinum(II), Pt-bpy, (SP-4-2)-dichlorido(1,10-phenanthroline) platinum(II), Pt-phen, and (SP-4-2)-chlorido(2,2':6',2''-terpyridine)platinum(II) chloride, Pt-terpy, on the aggregation of an amyloid model system derived from the C-terminal domain of Aß peptide (Aß21-40) were investigated. Thioflavin T (ThT) binding assays revealed the ability of Pt(II) compounds to repress amyloid aggregation in a dose-dependent way, whereas the ability of Aß21-40 peptide to interfere with ligand field of metal complexes was analyzed through UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. Spectroscopic data provided micromolar EC50 values and allowed to assess that the observed inhibition of amyloid aggregation is due to the formation of adducts between Aß21-40 peptide and complexes upon the release of labile ligands as chloride and that they can explore different modes of coordination toward Aß21-40 with respect to the entire Aß1-40 polypeptide. In addition, conformational studies through circular dichroism (CD) spectroscopy suggested that Pt-terpy induces soluble ß-structures of monomeric Aß21-40, thus limiting self-recognition. Noticeably, Pt-terpy demonstrated the ability to reduce the cytotoxicity of amyloid peptide in human SH-SY5Y neuroblastoma cells. Presented data corroborate the hypothesis to enlarge the application field of already known metal-based agents to neurodegenerative diseases, as potential neurodrugs.

Unsymmetric Cisplatin-Based Pt(IV) Conjugates Containing a PARP-1 Inhibitor Pharmacophore Tested on Malignant Pleural Mesothelioma Cell Lines.

Cisplatin is widely employed as a first-line chemotherapeutic agent for many solid tumors, including malignant pleural mesothelioma (MPM). However, its clinical use is limited by heavy side effects and acquired resistance, the latter being mainly related to enhanced DNA repair. Many clinical trials using combinations of platinum drugs and PARP-1 inhibitors (PARPis) have been carried out, with the hope that such combinations might lead to improved therapeutic efficacy against tumors. Here, the synthesis and efficacy in reducing MPM cell viability of four cisplatin-based Pt(IV) prodrugs containing the PARPi 3-aminobenzamide (3-ABA) fragment are described. The most promising conjugate is more effective than cisplatin or cisplatin/3-ABA combination, administered in equimolar doses, in inhibiting PARP-1 activity and inducing apoptosis in BRCA1/2 wild type MPM cells, grown as monolayer or as multicellular spheroids.

A multi-methodological inquiry of the behavior of cisplatin-based Pt(IV) derivatives in the presence of bioreductants with a focus on the isolated encounter complexes.

The study of Pt(IV) antitumor prodrugs able to circumvent some drawbacks of the conventional Pt(II) chemotherapeutics is the focus of a lot of attention. This paper reports a thorough study based on experimental methods (reduction kinetics, electrochemistry, tandem mass spectrometry and IR ion spectroscopy) and quantum-mechanical DFT calculations on the reduction mechanism of cisplatin-based Pt(IV) derivatives having two hydroxido (1), one hydroxido and one acetato (2), or two acetato ligands (3) in axial position. The biological reductants glutathione and ascorbic acid were taken into consideration. The presence of a hydroxido ligand resulted to play an important role in the chemical reduction with ascorbic acid, as verified by 15N-NMR kinetic analysis using 15N-enriched complexes. The reactivity trend (1 > 2 > 3) does not reflect the respective reduction peak potentials (1 < 2 < 3), an inverse relationship already documented in similar systems. Turning to a simplified environment, the Pt(IV) complexes associated with a single reductant molecule (corresponding to the encounter complex occurring along the reaction coordinate in bimolecular reactions in solution) were characterized by IR ion spectroscopy and sampled for their reactivity under collision-induced dissociation (CID) conditions. The complexes display a comparable reduction reactivity ordering as that observed in solution. DFT calculations of the free energy pathways for the observed fragmentation reactions provide theoretical support for the CID patterns and the mechanistic hypotheses on the reduction process are corroborated by the observed reaction paths. The bulk of these data offers a clue of the intricate pathways occurring in solution.Graphic abstract.

Can an Elusive Platinum(III) Oxidation State be Exposed in an Isolated Complex?

Platinum(IV) complexes are extensively studied for their activity against cancer cells as potential substitutes for the widely used platinum(II) drugs. PtIV complexes are kinetically inert and need to be reduced to PtII species to play their pharmacological action, thus acting as prodrugs. The mechanism of the reduction step inside the cell is however still largely unknown. Gas-phase activation of deprotonated platinum(IV) prodrugs was found to generate products in which platinum has a formal +3 oxidation state. IR multiple photon dissociation spectroscopy is thus used to obtain structural information helping to define the nature of both the platinum atom and the ligands. In particular, comparison of calculations at DFT, MP2 and CCSD levels with experimental results demonstrates that the localization of the radical is about equally shared between the dxz orbital of platinum and the pz of nitrogen on the amino group, the latter acting as a non-innocent ligand.

Antiproliferative Activity of Pt(IV) Conjugates Containing the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Ketoprofen and Naproxen †.

Cisplatin and several non-steroidal anti-inflammatory drugs (NSAIDs) have been proven to act synergistically or at least additively on several tumor cell lines. Dual-action cisplatin-based Pt(IV) combos containing ketoprofen and naproxen offer good antiproliferative performance on a panel of human tumor cell lines, including a malignant pleural mesothelioma (MPM) one, a very chemoresistant tumor. The main reason of the increased activity relies on the enhanced lipophilicity of these Pt(IV) conjugates that in turn promotes increased cellular accumulation. A quick Pt(IV)→Pt(II) reduction generates the active cisplatin metabolite. The NSAID adjuvant action seems to be almost independent from cyclooxygenase-2 (COX-2) expression in the tumor cells under investigation (lung A-549, colon HT-29, HCT 116, SW480, ovarian A2780, and biphasic MPM MSTO-211H), but it seems to rely (at least in part) on the activation of the NSAID activated gene, NAG-1 (a member of the transforming growth factor beta, TGF-ß, superfamily), which has been suggested to be involved in NSAID antiproliferative activity.

A new entry to asymmetric platinum(IV) complexes via oxidative chlorination.

Pt(IV) complexes are usually prepared by oxidation of the corresponding Pt(II) counterparts, typically using hydrogen peroxide or chlorine. A different way to synthesize asymmetrical Pt(IV) compounds is the oxidative chlorination of Pt(II) counterparts with N-chlorosuccinimide. The reaction between cisplatin cis-[PtCl2(NH3)2], carboplatin, cis-[PtCl2(dach)] and cis-[Pt(cbdc)(dach)] (cbdc = cyclobutane-1,1'-dicarboxylato; dach = cyclohexane-1R,2R-diamine) with N-chlorosuccinimide in ethane-1,2-diol was optimized to produce the asymmetric Pt(IV) octahedral complexes [PtA2Cl(glyc)X2] (A2 = 2 NH3 or dach; glyc = 2-hydroxyethanolato; X2 = 2 Cl or cbdc) in high yield and purity. The X-ray crystal structure of the [Pt(cbdc)Cl(dach)(glyc)] complex is also reported. Moreover, the oxidation method proved to be versatile enough to produce other mixed Pt(IV) derivatives varying the reaction medium. The two trichlorido complexes easily undergo a pH-dependent hydrolysis reaction, whereas the dicarboxylato compounds are stable enough to allow further coupling reactions for drug targeting and delivery via the glyc reactive pendant. Therefore, the coupling reaction between the [Pt(cbdc)Cl(dach)(glyc)] and a model carboxylic acid, a model amine, and selectively protected amino acids is reported.

Study of the synthesis, antiproliferative properties, and interaction with DNA and polynucleotides of cisplatin-like Pt(II) complexes containing carcinogenic polyaromatic amines.

The chemical and biological features of two newly synthesized [PtCl2(L)(2-aminonaphthalene)] complexes (L is NH3 or 2-aminonaphthalene) were compared with those of two already reported enantiomeric complexes of formula [PtCl2(DABN)] [DABN is (R)-1,1'-binaphthyl-2,2'-diamine or (S)-1,1'-binaphthyl-2,2'-diamine]. Solution behavior, lipophilicity, cytotoxicity with regard to one colorectal (HCT116) and two ovarian (A2780 and A2780Cp8) human carcinoma cell lines, and in vitro DNA- and G-quadruplex-binding properties were evaluated. In particular, the cytotoxicity of [PtCl2(NH3)(2-aminonaphthalene)] was better than that of cisplatin for all cell lines, and rather resembled that of oxaliplatin. The solution behavior of the whole series of complexes and the absence of an evident relationship between lipophilicity and cytotoxicity seem to suggest that all these experimental parameters are probably smoothed out during the 3-day cytotoxicity experiments and do not strongly affect the half-maximal inhibitory concentrations. The results of electrophoretic studies indicate that different kinds of interaction with DNA can be involved in the mode of action of these complexes, with intercalation in double-stranded DNA and stacking on G-quadruplex DNA being strongly implicated in particular for [PtCl2(NH3)(2-aminonaphthalene)].

Platinum(IV) combo prodrugs containing cyclohexane-1R,2R-diamine, valproic acid, and perillic acid as a multiaction chemotherapeutic platform for colon cancer.

The complex [PtCl2(cyclohexane-1R,2R-diamine)] has been combined in a Pt(IV) molecule with two different bioactive molecules (i.e., the histone deacetylase inhibitor 2-propylpentanoic acid or valproic acid, VPA, and the potential antimetastatic molecule 4-isopropenylcyclohexene-1-carboxylic acid or perillic acid, PA) in order to obtain a set of multiaction or multitarget antiproliferative agents. In addition to traditional thermal synthetic procedures, microwave-assisted heating was used to speed up their preparation. All Pt(IV) complexes showed antiproliferative activity on four human colon cancer cell lines (namely HCT116, HCT8, RKO and HT29) in the nanomolar range, considerably better than those of [PtCl2(cyclohexane-1R,2R-diamine)], VPA, PA, and the reference drug oxaliplatin. The synthesized complexes showed pro-apoptotic and pro-necrotic effects and the ability to induce cell cycle alterations. Moreover, the downregulation of histone deacetylase activity, leading to an increase in histone H3 and H4 levels, and the antimigratory activity, indicated by the reduction of the levels of matrix metalloproteinases MMP2 and MMP9, demonstrated the multiaction nature of the complexes, which showed biological properties similar to or better than those of VPA and PA, but at lower concentrations, probably due to the lipophilicity of the combo molecule that increases the intracellular concentration of the single components (i.e., [PtCl2(cyclohexane-1R,2R-diamine)], VPA and PA).

The inhibitory effects of platinum(II) complexes on amyloid aggregation: a theoretical and experimental approach.

Platinum (Pt)(II) square planar complexes are well-known anticancer drugs whose Mechanism of Action (MOA) are finely tuned by the polar, hydrophobic and aromatic features of the ligands. In the attempt to translate this tunability to the identification of potential neurodrugs, herein, four Pt(II) complexes were investigated in their ability to modulate the self-aggregation processes of two amyloidogenic models: Sup35p7-13 and NPM1264-277 peptides. In particular, phenanthriplatin revealed the most efficient agent in the modulation of amyloid aggregation: through several biophysical assays, as Thioflavin T (ThT), electrospray ionization mass spectrometry (ESI-MS) and ultraviolet-visible (UV-vis) absorption spectroscopy, this complex revealed able to markedly suppress aggregation and to disassemble small soluble aggregates. This effect was due to a direct coordination of phenanthriplatin to the amyloid, with the loss of several ligands and different stoichiometries, by the formation of π-π and π-cation interactions as indicated from molecular dynamic simulations. Presented data support a growing and recent approach concerning the repurposing of metallodrugs as potential novel neurotherapeutics.

Image-Guided Nanodelivery of Pt(IV) Prodrugs to GRP-Receptor Positive Tumors.

Over the last decades, gold nanoparticles (AuNPs) have proven to be remarkable tools for drug delivery and theranostic applications in cancer treatment. On the other hand, Pt(IV) prodrugs have been employed as an interesting alternative to the more common Pt(II) complexes, such as cisplatin, for cancer chemotherapy. Searching to design an image-guided nanocarrier to deliver selectively Pt(IV) prodrugs to tumors expressing the gastrin releasing peptide receptor (GRPR), we have synthesized small core AuNPs carrying a thiolated DOTA derivative, a GRPR-targeting bombesin analog (BBN[7-14]) and a Pt(IV) prodrug attached to the AuNPs without (AuNP-BBN-Pt1) or with a PEGylated linker (AuNP-BBN-Pt2 and AuNP-BBN-Pt3). In the GRPR+ prostate cancer PC3 cell line, the cytotoxic activity of the designed AuNP-BBN-Pt nanoparticles is strongly influenced by the presence of the PEGylated linker. Thus, AuNP-BBN-Pt1 displayed the lowest IC50 value (9.3 ± 2.3 µM of Pt), which is comparable to that exhibited by cisplatin in the same cell line. In contrast, AuNP-BBN-Pt1 showed an IC50 value of 97 ± 18 µM of Pt in the non-tumoral RWPE-1 prostate cells with a much higher selective index (SI) towards PC3 cells (SI = 10) when compared with cisplatin (SI = 1.3). The AuNPs were also successfully labeled with 67Ga and the resulting 67Ga-AuNP-BBN-Pt were used to assess their cellular uptake in PC3 cells, with AuNP-BBN-Pt1 also displaying the highest cellular internalization. Finally, intratumoral administration of 67Ga-AuNP-BBN-Pt1 in a PC3 tumor-bearing mice showed a prolonged retention of the nanoparticle compared to that of cisplatin, with optimal in vivo stability and 20% of the injected platinum remaining in the tumor after 72 h post-injection. Furthermore, microSPECT imaging studies confirmed the uptake and considerable retention of the 67Ga-labeled AuNPs in the tumors. Overall, these results show the potential of these targeted AuNPs loaded with Pt(IV) prodrugs for prostate cancer theranostics.

Synthesis and biological studies of pyrazolyl-diamine Pt(II) complexes containing polyaromatic DNA-binding groups.

New [PtCl(pz*NN)](n+) complexes anchored by pyrazolyl-diamine (pz*NN) ligands incorporating anthracenyl or acridine orange DNA-binding groups have been synthesized so as to obtain compounds that would display synergistic effects between platination and intercalation of DNA. Study of their interaction with supercoiled DNA indicated that the anthracenyl-containing complex L(2) Pt displays a covalent type of binding, whereas the acridine orange counterpart L(3) Pt shows a combination of intercalative and covalent binding modes with a strong contribution from the former. L(2) Pt showed a very strong cytotoxic effect on ovarian carcinoma cell lines A2780 and A2780cisR, which are, respectively, sensitive to and resistant to cisplatin. In these cell lines, L(2) Pt is nine to 27 times more cytotoxic than cisplatin. In the sensitive cell line, L(3) Pt showed a cytotoxic activity similar to that of cisplatin, but like L(2) Pt was able significantly to overcome cisplatin cross-resistance. Cell-uptake studies showed that L(2) Pt accumulates preferentially in the cytoplasm, whereas L(3) Pt reaches the cell nucleus more easily, as clearly visualized by time-lapse confocal imaging of live A2870 cells. Altogether, these findings seem to indicate that interaction with biological targets other than DNA might be involved in the mechanism of action of L(2) Pt because this compound, despite having a weaker ability to target the cell nucleus than L(3) Pt, as well as an inferior DNA affinity, is nevertheless more cytotoxic. Furthermore, ultrastructural studies of A2870 cells exposed to L(2) Pt and L(3) Pt revealed that these complexes induce different alterations in cell morphology, thus indicating the involvement of different modes of action in cell death.

Pt(IV) antitumor prodrugs: dogmas, paradigms, and realities.

Platinum(II)-based drugs are widely used for the treatment of solid tumors, especially in combination protocols. Severe side effects and occurrence of resistance are the major limitations to their clinical use. To overcome these drawbacks, a plethora of Pt(IV) derivatives, acting as anticancer prodrugs, have been designed, synthesized and preclinically (often only in vitro) tested. Here, we summarize the recent progress in the development and understanding of the chemical properties and biochemical features of these Pt(IV) prodrugs, especially those containing bioactive molecules as axial ligands, acting as multi-functional agents. Even though no such prodrugs have been yet approved for clinical use, many show encouraging pharmacological profiles. Thus, a better understanding of their features is a promising approach towards improving the available Pt-based anticancer agents.

Application of the anthraquinone drug rhein as an axial ligand in bifunctional Pt(IV) complexes to obtain antiproliferative agents against human glioblastoma cells.

Octahedral Pt(IV) prodrugs are an effective way to combine cisplatin-like moieties and a second drug to obtain selective and stimuli responsive bifunctional antiproliferative compounds. Recently, two bifunctional Pt(IV) complexes have shown interesting in vitro and in vivo effects in glioblastoma, the most aggressive primary brain tumor. An interesting observation indicates that 4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylic acid (rhein) can inhibit in vivo glioma tumor progression. Furthermore, a prodrug in which cisplatin was combined with two molecules of rhein showed a potency higher than that of cisplatin toward cisplatin-resistant lung carcinoma cells. However, the high lipophilicity of this type of complex affects their solubility and bioavailability. To overcome these limits, in the present work, three Pt(IV) derivatives were obtained by differently linking one molecule of rhein and one acetato ligand at the axial position to a cisplatin core. The complexes proved to be similar to or more potent than the parent cisplatin and rhein, and the reference drug temozolomide on two human glioblastoma cell lines (U87-MG and T98G). They retained their activity under hypoxia and caused a significant reduction in the motility of both cell lines, which can be related to their ability to inhibit MMP2 and MMP9 matrix metalloproteinases. Finally, physicochemical and computational studies indicated that these Pt(IV) derivatives are more prone than rhein to cross the blood-brain barrier.

The Strange Case: The Unsymmetric Cisplatin-Based Pt(IV) Prodrug [Pt(CH3COO)Cl2(NH3)2(OH)] Exhibits Higher Cytotoxic Activity with respect to Its Symmetric Congeners due to Carrier-Mediated Cellular Uptake.

The biological behavior of the axially unsymmetric antitumor prodrug (OC-6-44)-acetatodiamminedichloridohydroxidoplatinum(IV), 2, was deeply investigated and compared with that of analogous symmetric Pt(IV) complexes, namely, dihydroxido 1 and diacetato 3, which have a similar structure. The complexes were tested on a panel of human tumor cell lines. Complex 2 showed an anomalous higher cytotoxicity (similar to that of cisplatin) with respect to their analogues 1 and 3. Their reduction potentials, reduction kinetics, lipophilicity, and membrane affinity are compared. Cellular uptake and DNA platination of Pt(IV) complexes were deeply investigated in the sensitive A2780 human ovarian cancer cell line and in the corresponding resistant A2780cisR subline. The unexpected activity of 2 appears to be related to its peculiar cellular accumulation and not to a different rate of reduction or a different efficacy in DNA platination and/or efficiency in apoptosis induction. Although the exact mechanism of cell uptake is not fully deciphered, a series of naïve experiments indicates an energy-dependent, carrier-mediated transport: the organic cation transporters (OCTs) are the likely proteins involved.

The power of a novel combined anticancer therapy: challenge and opportunity of micotherapy in the treatment of Glioblastoma Multiforme.

Glioblastoma (GBM) is the most common and mortal primary brain tumor in human. After standard therapies, that include surgical resection followed by radiotherapy and chemotherapy, it is difficult to completely remove the tumor and the development of relapses and resistance is almost inevitable. The chemotherapy now available also show important side effects, to overcame those limitation, new platinum-based drugs are being synthetized, Pt(IV)Ac-POA, (OC-6-44)-acetate-diamine-chloride(2-(2-propynyl)octanoato)platinum(IV), a prodrug having an Histone-3-DeAcetylase-Inhibitor as axial ligands, is one of them. Moreover, new compounds of plant origin are increasingly seen as potential sources of benefits in oncological treatments. The aim of the study is to investigate the possible contribution of micotherapy in the fight against GBM, its role in the metabolism of reactive oxygen species (ROS) and its synergic effect with a new platinum-based compound, Pt(IV)Ac-POA, on human glioblastoma U251 cells. Through cytofluorimetric and immunofluorescence analysis, the ability of the micotherapy in study to regulate the cell cycle was assessed, and its importance in controlling the cellular redox state was also revealed, opening to the possibility of a new therapy in which micotherapy can support the activity of new chemotherapy while reducing its side effects controlling inflammatory conditions in the microenvironment. Additionally, the combined therapy appeared able to induce regulated form of necrosis, such as ferroptosis, and to hinder the establishment of resistance mechanisms.

Molecular and statistical modeling of reduction peak potential and lipophilicity of platinum(IV) complexes.

We report the results of the quantitative structure-property relationship analysis of 31 Pt(IV) complexes, for three of which the synthesis is reported for the first time. The X-ray structural analysis of one complex of the series was performed to demonstrate that the PM6 semiempirical method satisfactorily reproduces key features of the geometry of the complexes investigated. Molecular properties extracted from such calculations were then used to construct models of experimental data such as electrochemical peak potentials (evaluated by cyclic voltammetry) and the octanol-water partition coefficient (evaluated by a reversed-phase high performance liquid chromatography method), which are key aspects in the design of such Pt(IV) complexes as potential anticancer prodrugs. Statistically accurate models for both properties were found using combinations of surface areas, orbital energies, dipole moments, and atomic partial charges. These models could form the basis of virtual screening of potential drug molecules, allowing the prediction of properties, closely related to the antiproliferative activity of Pt(IV) complexes, directly from calculated data.

Studies on log Po/w of quinoxaline di-N-oxides: a comparison of RP-HPLC experimental and predictive approaches.

As reported in our previous papers, a series of quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives were synthesized and studied as anti-tuberculosis agents. Here, the capability of the shake-flask method was studied and the retention time (expressed as log K) of 20 compounds were determined by RP-HPLC analysis. We found that the prediction of log P by the RP-HPLC analysis can result in a high accuracy and can replace the shake-flask method avoiding the experimental problems presented by quinoxaline di-N-oxides. The studied compounds were subjected to the ALOGPS module with the aim of comparing experimental log P(o/w) values and predicted data. Moreover, a preliminary in silico screening of the QSAR relationship was made confirming the influence of reduction peak potential, lipophilicity, H-bond donor capacity and molecular dimension descriptors on anti-tuberculosis activity.