Synthesis, spectral characterisation, biocidal investigation, in-silico and molecular docking studies of 4-[(2-chloro-4-methylphenyl)carbamoyl]butanoic acid derived triorganotin(IV) compounds.

Three triorganotin(IV) compounds, R3Sn(L), with R = CH3 (1), n-C4H9 (2) and C6H5 (3), and LH = 4-[(2-chloro-4-methylphenyl)carbamoyl]butanoic acid, were prepared and confirmed by various techniques. A five-coordinate, distorted trigonal-bipyramidal geometry was elucidated for tin(IV) centres both in solution and solid states. An intercalation mode was confirmed for the compound SS-DNA interaction by UV-visible, viscometric techniques and molecular docking. MD simulation revealed stable binding of LH with SS-DNA. Anti-bacterial investigation revealed 2 to be generally the most potent, especially against Sa and Ab, i.e. having the lowest MIC values (≤0.25 µg/mL) compared to the standard anti-biotics vancomycin-HCl (MIC = 1 µg/mL) and colistin-sulphate (MIC = 0.25 µg/mL). Similarly, the anti-fungal profile shows 2 exhibits 100% inhibition against Ca and Cn fungal strains and has MIC values (≤0.25 µg/mL) comparatively lower than standard drug fluconazole (0.125 and 8 µg/mL for Ca and Cn, respectively). Compound 2 has the greatest activity with CC50 ≤ 25 µg/mL and HC50 > 32 µg/mL performed against HEC239 and RBC cell lines. The anti-cancer potential was assessed against the MG-U87 cell line, using cisplatin as the standard (133 µM), indicates 2 displays the greatest activity (IC50: 5.521 µM) at a 5 µM dose. The greatest anti-leishmanial potential was observed for 2 (87.75 at 1000 µg/mL) in comparison to amphotericin B (90.67). The biological assay correlates with the observed maximum of 89% scavenging activity exhibited by 2. The Swiss-ADME data publicised the screened compounds generally follow the rule of 5 of drug-likeness and have good bioavailability potential.

Designing and Exploration of the Biological Potentials of Novel Centrosymmetric Heteroleptic Copper(II) Carboxylates.

Copper(II) complexes with a general formula [Cu2(3,4-F2C6H3CH2COO)4(L)2], where L = 2-methylpyridine (1) and 3-methylpyridine (2), are reported here. The FTIR spectra of the complexes confirmed the bridging bidentate coordination mode of the carboxylate ligand. The low (475 and 449 cm-1) and strong (727 & 725 cm-1) intensity bands in the FTIR spectra, due to Cu-N stretches and pyridyl ring vibrations, confirmed coordination of the 2-/3-methyl pyridine co-ligands in complexes 1 and 2, respectively. A binuclear paddlewheel structural arrangement with a square pyramidal geometry was confirmed for copper atoms in the complexes via single-crystal X-ray analysis. The DPPH, •OH radical, and α-amylase enzyme inhibition assays showed higher activities for the complexes than for the free ligand acid. The binding constant (Kb = 1.32 × 105 for 1 and 5.33 × 105 for 2) calculated via UV-VIS absorption measurements and docking scores (-6.59 for 1 and -7.43 for 2) calculated via molecular docking showed higher SS-DNA binding potential for 2 compared to 1. Viscosity measurement also reflected higher DNA binding ability for 2 than 1. Both complexes 1 and 2 (docking scores of -7.43 and -6.95, respectively) were found to be more active inhibitors than the free ligand acid (docking score of -5.5159) against the target α-amylase protein. This in silico study has shown that the herein reported compounds follow the rules of drug-likeness and exhibit good potential for bioavailability.

Synthesis, Physicochemical Characterization, Biological Evaluation, In Silico and Molecular Docking Studies of Pd(II) Complexes with P, S-Donor Ligands.

One homoleptic (1) and three heteroleptic (2-4) palladium(II) complexes were synthesized and characterized by various physicochemical techniques, i.e., elemental analysis, FTIR, Raman spectroscopy, 1H, 13C, and 31P NMR. Compound 1 was also confirmed by single crystal XRD, showing a slightly distorted square planar geometry. The antibacterial results obtained via the agar-well diffusion method for compound 1 were maximum among the screen compounds. All the compounds have shown good to significant antibacterial results against the tested bacterial strains, Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus, except 2 against Klebsiella pneumonia. Similarly, the molecular docking study of compound 3 has shown the best affinity with binding energy scores of -8.6569, -6.5716, and -7.6966 kcal/mol against Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus, respectively. Compound 2 has exhibited the highest activity (3.67 µM), followed by compound 3 (4.57 µM), 1 (6.94 µM), and 4 (21.7 µM) against the DU145 human prostate cancer cell line using the sulforhodamine B (SRB) method as compared to cisplatin (>200 µM). The highest docking score was obtained for compounds 2 (-7.5148 kcal/mol) and 3 (-7.0343 kcal/mol). Compound 2 shows that the Cl atom of the compound acts as a chain side acceptor for the DR5 receptor residue Asp B218 and the pyridine ring is involved in interaction with the Tyr A50 residue via arene-H, while Compound 3 interacts with the Asp B218 residue via the Cl atom. The physicochemical parameters determined by the SwissADME webserver revealed that no blood-brain barrier (BBB) permeation is predicted for all four compounds, while gastrointestinal absorption is low for compound 1 and high for the rest of the compounds (2-4). As concluding remarks based on the obtained in vitro biological results, the evaluated compounds after in vivo studies might be a good choice for future antibiotics and anticancer agents.

Synthesis, Structural Elucidation and Pharmacological Applications of Cu(II) Heteroleptic Carboxylates.

Six heteroleptic Cu(II) carboxylates (1-6) were prepared by reacting 2-chlorophenyl acetic acid (L1), 3-chlorophenyl acetic acid (L2), and substituted pyridine (2-cyanopyridine and 2-chlorocyanopyridine). The solid-state behavior of the complexes was described via vibrational spectroscopy (FT-IR), which revealed that the carboxylate moieties adopted different coordination modes around the Cu(II) center. A paddlewheel dinuclear structure with distorted square pyramidal geometry was elucidated from the crystal data for complexes 2 and 5 with substituted pyridine moieties at the axial positions. The presence of irreversible metal-centered oxidation reduction peaks confirms the electroactive nature of the complexes. A relatively higher binding affinity was observed for the interaction of SS-DNA with complexes 2-6 compared to L1 and L2. The findings of the DNA interaction study indicate an intercalative mode of interaction. The maximum inhibition against acetylcholinesterase enzyme was caused for complex 2 (IC50 = 2 µg/mL) compared to the standard drug Glutamine (IC50 = 2.10 µg/mL) while the maximum inhibition was found for butyrylcholinesterase enzyme by complex 4 (IC50 = 3 µg/mL) compared to the standard drug Glutamine (IC50 = 3.40 µg/mL). The findings of the enzymatic activity suggest that the under study compounds have potential for curing of Alzheimer's disease. Similarly, complexes 2 and 4 possess the maximum inhibition as revealed from the free radical scavenging activity performed against DPPH and H2O2.

A Broad Spectrum Antiparasitic Activity of Organotin (IV) Derivatives and Its Untargeted Proteomic Profiling Using Leishmania donovani.

Metals have been used in medicine since ancient times for the treatment of different ailments with various elements such as iron, gold and arsenic. Metal complexes have also been reported to show antibiotic and antiparasitic activity. In this context, we tested the antiparasitic potential of 10 organotin (IV) derivatives from 4-(4-methoxyphenylamino)-4 oxobutanoic acid (MS26) against seven eukaryotic pathogens of medical importance: Leishmania donovani, Trypanosoma cruzi, Trypanosoma brucei, Entamoeba histolytica, Giardia lamblia, Naegleria fowleri and Schistosoma mansoni. Among the compounds with and without antiparasitic activity, compound MS26Et3 stood out with a 50% effective concentration (EC50) of 0.21 and 0.19 µM against promastigotes and intracellular amastigotes of L. donovani, respectively, 0.24 µM against intracellular amastigotes of T. cruzi, 0.09 µM against T. brucei, 1.4 µM against N. fowleri and impaired adult S. mansoni viability at 1.25 µM. In terms of host/pathogen selectivity, MS26Et3 demonstrated relatively mild cytotoxicity toward host cells with a 50% viability concentration of 4.87 µM against B10R cells (mouse monocyte cell line), 2.79 µM against C2C12 cells (mouse myoblast cell line) and 1.24 µM against HEK923 cells (human embryonic kidney cell line). The selectivity index supports this molecule as a therapeutic starting point for a broad spectrum antiparasitic alternative. Proteomic analysis of host cells infected with L. donovani after exposure to MS26Et3 showed a reduced expression of Rab7, which may affect the fusion of the endosome with the lysosome, and, consequently, impairing the differentiation of L. donovani to the amastigote form. Future studies to investigate the molecular target(s) and mechanism of action of MS26Et3 will support its chemical optimization.

Synthesis, Characterization, Biological Activity and Molecular Docking Studies of Novel Organotin(IV) Carboxylates.

Four new carboxylates complexes with general formula R2SnL2 and R3SnL, where R = n-butyl (1, 3), methyl (2, 4) and L = 4-Chlorophenoxyacetate, were synthesized in significant yields. FT-IR analysis revealed a chelating (1 and 2) and a bridging bidentate (3 and 4) coordination modes for the carboxylate ligand in solid state which was further confirmed by the single crystal X-ray analysis of complex 4. The NMR data (1H, 13C and 119Sn) revealed a higher coordination number around the tin center in R2SnL2 (1 and 2) compared to R3SnL (3 and 4). A close matching was observed between the experimental and calculated structures (obtained at B3LYP/6-31G* + LANL2DZ basis set). Quantum chemical analysis indicates that the carboxylate moiety has the major contribution in the formation of filled and unfilled orbitals as well as in ligand to ligand intramolecular charge transfer during the electronic transitions. The cytotoxicity data of the screened compounds evaluated against lung cancer cell line (A549) and normal lung fibroblast cell line (MRC-5) revealed that 1, 3 and 4 have shown dose dependent cytotoxic effects while HL and 2 have shown steady and low cytotoxic activities. The antibacterial activity of complexes 1-4 is higher than that of HL. Molecular docking study showed an intercalation binding mode for complex 3 with DNA (docking score = -3.6005) involving four polar interactions. Complex 3 docking with tubulin (PDB ID 1SA0) with colchicine as a target protein resulted in three polar interactions (docking score -5.2957). Further, the docking analysis of the HL and 1-4 has shown an adequate interactions with the coronavirus SARS-CoV-2 spike protein, nucleocapsid protein and human angiotensin converting enzyme (ACE2).

Zinc metal carboxylates as potential anti-Alzheimer's candidate: in vitro anticholinesterase, antioxidant and molecular docking studies.

In search of suitable therapy for the management of Alzheimer's disease, this study was designed to evaluate metal complexes against its biochemical targets. Zinc metal carboxylates (AAZ1-AAZ6) were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The antioxidant in combination with anticholinesterase activity can be considered as an important target in the management of Alzheimer's disease. Therefore, these compounds were also screened for ABTS and DPPH free radical scavenging activity. In AChE inhibition assay, we noticed encouraging IC50 values of 33.07 and 59.52 µM for compounds AAZ5 and AAZ3, respectively. However, when we tested BChE activity, we observed an outstanding IC50 of 0.056 µM for compound AAZ6. Amazingly all of our compounds (AAZ1-AAZ6) were proved to be strong antioxidants which actively supplement the anti-Alzheimer's activity. The majority of our compounds exhibited lower IC50 values than the standard ascorbic acid in both DPPH and ABTS assays. We also correlated our results with molecular docking studies. Results elaborated that AAZ1 and AAZ5 exhibit strong interactions with amino acids HIS 362, HIS 398, GLU 306 ARG 289 and SER 237 inside binding pocket of targeted protein. In remarks, we can claim that our synthesized zinc metal carboxylates have strong potency to manage Alzheimer's disease on both anticholinesterase and antioxidant targets. Communicated by Ramaswamy H. Sarma.

Spectroscopic characterizations, structural peculiarities, molecular docking study and evaluation of biological potential of newly designed organotin(IV) carboxylates.

In the search for new therapeutic agents we have synthesized 13 new organotin(IV) carboxylate derivatives of (E)-4-((4-methoxy-2-nitrophenyl)amino)-4-oxobut-2-enoic acid. The synthesized complexes were characterized by several spectroscopic techniques. A chelating or bridging bidentate nature of the carboxylate ligand was suggested from the solid state FT-IR results. Solution state multinuclear NMR (1H, 13C and 119Sn) results reveal that the geometry around the Sn atom in triorganotin(IV) complexes is trigonal bipyramidal and in diorganotin(IV) complexes is octahedral. The ligand, (E)-4-((4-methoxy-2-nitrophenyl)amino)-4-oxobut-2-enoic acid, complex 1 and complex 2 were also analyzed by single crystal X-ray technique and the results fully supports the spectroscopic data. For 1 and 2 the geometry optimized by the single crystal X-ray analyses is distorted trigonal bipyramidal. The interaction of the studied compounds with SS-DNA was investigated by UV-Vis. Spectroscopy and Molecular docking showing an intercalative mode of binding. The evaluation of the screened compounds for cancer treatment displays even higher than that of the vincristine used as a standard drug. Similarly the performance of the tested compounds as an antileishmanial agent considers them very close in activity to the standard drug, amphotericin B. The antibacterial results show that the most of the compounds have a moderate sensitivity against the studied bacterial pathogens.

Newly designed organotin(IV) carboxylates with peptide linkage: Synthesis, structural elucidation, physicochemical characterizations and pharmacological investigations.

Fourteen new organotin(IV) carboxylate complexes with peptide linkage of (2-(4-methoxy-2-nitrophenylcarbamoyl)benzoic acid) were successfully synthesized and characterized by elemental analyses, FT-IR, NMR (1H, 13C and 119Sn) and single crystal X-ray techniques. FT-IR results of the sodium salt of 2-(4-methoxy-2-nitrophenylcarbamoyl)benzoic acid and complexes showed that the coordination took place via oxygen atoms of the carboxylate group. 1J(119Sn-13C), 2J(119Sn-1H) and θ values calculated from 1H and 13C NMR data using Lockhart's equation reveal a trigonal bipyramidal geometry for triorganotin(IV) derivatives and an octahedral geometry for diorganotin(IV) derivatives. Crystallographic data for three triorganotin(IV) complexes (1-3) showed the tin has distorted trigonal bipyramidal geometry. In vitro anticancer activity against lung carcinoma (H-157) and kidney fibroblast (BHK-21) cell lines as well as antileishmanial activity against the promastigote forms of leishmania major of the synthesized compounds were also studied and the complexes were found biologically active. The in vitro antibacterial activity of most of the synthesized organotin(IV) derivatives against the studied bacterial pathogens is higher than those of the standard 3rd generation antibiotics such as Tetracycline, Penicillin G, Ampicillin, Amoxicillin. This suggest the use of these newly designed organotin(IV) derivatives as potent antibiotics. The synthesized compounds interact with DNA via intercalative mode of interaction. Viscosity measurement results also support the intercalative mode of interaction for the compounds with DNA.

Design, Synthesis, in vitro Antiproliferative Activity, Binding Modeling of 1,2,4,-Triazoles as New Anti-Breast Cancer Agents.

This article demonstrates the synthesis of 1,2,4-triazole derivatives and their applications in medicine particularly as anti-breast cancer agents which is a major issue of the present. The synthesized compounds were characterized by elemental analysis, FT-IR and NMR. DFT was used to study the quantum chemical calculations of geometries and vibrational wave numbers of 3-hydroxynaphthyl and p-tolyl substituted 1,2,4-triazoles in the ground state. The scaled harmonic vibrational frequencies obtained from the DFT method were compared with those of the FT-IR spectra and found good agreement. The synthesized 1,2,4-triazole-naphthyl hybrids were screened for the anticancer activity against MCF-7 breast cancer lines. Among them compounds 3 and 7 showed broad spectrum anticancer activity with IC50 values 9.7 µM and 7.10 µM, respectively and their activity is comparable to that of the standard drugs. The molecular model for binding between the compounds (1-8) and the active site of BRCA2 was obtained on the basis of the computational docking results and the structure-activity relationship.

Organotin(IV) Carboxylates as Promising Potential Drug Candidates in the Field of Cancer Chemotherapy.

Medicinal inorganic chemistry plays an important role in exploring the properties of metal ions for the designing of new drugs. The field has been stimulated by the success of cis-platin, the world best selling anticancer drug and platinum complexes with reduced toxicity, oral activity and activity against resistant tumors are currently on clinical trial. The use of cis-platin is, however, severely limited by its toxic side-effects. This has stimulated chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. The discovery of new non-covalent interactions with the classical target, DNA, was the first developing step in the treatment of cancer. The use of organometallic compounds as a medicine is very common now a days because it offers potential advantages over the more common organic-based drugs. In this article we have highlighted the anticancer activity of the organotin(IV) carboxylates published in the last few years (from 2008 to 2016). In most cases they present lower IC50 values than those of cisplatin, which indicates their high activity against the cancer cell lines. The summarized data reveal that every year new organotin(IV) carboxylate complexes are synthesized with the aim of new anticancer agent with much better results than the than the corresponding activity of cis-platin or other clinically approved drugs. In addition to the advantages of high activity, compared to the platinum compound, tin complexes are much cheaper. Thus by using organotin carboxylate for clinical medicine, cost reduction, dosage reduction and effect enhancement will be reached.

Photo-induced Leishmania DNA degradation by silver-doped zinc oxide nanoparticle: an in-vitro approach.

Recently, the authors reported newly synthesised polyethylene glycol (PEG)ylated silver (9%)-doped zinc oxide nanoparticle (doped semiconductor nanoparticle (DSN)) which has high potency for killing Leishmania tropica by producing reactive oxygen species on exposure to sunlight. The current report is focused on Leishmania DNA interaction and damage caused by the DSN. Here, we showed that the damage to Leishmania DNA was indirect, as the DSN was unable to interact with the DNA in intact Leishmania cell, indicating the incapability of PEGylated DSN to cross the nucleus barrier. The DNA damage was the result of high production of singlet oxygen on exposure to sunlight. The DNA damage was successfully prevented by singlet oxygen scavenger (sodium azide) confirming involvement of the highly energetic singlet oxygen in the DNA degradation process.

Pharmacological investigations and Petra/Osiris/Molinspiration (POM) analyses of newly synthesized potentially bioactive organotin(IV) carboxylates.

A series of organotin(IV) carboxylate complexes: [Me2SnL2] (1), [n-Bu2SnL2] (2), [n-Oct2SnL2] (3), [Me3SnL] (4), [n-Bu3SnL] (5) and [Ph3SnL] (6), where L=3-(4-fluorophenyl)acrylic acid, have been successfully synthesized and characterized by FT-IR, NMR ((1)H, (13)C) and single crystal analysis. The ligand coordinates to tin atom via carboxylate group. Compound 4 was also analyzed by single crystal XRD analysis. Crystallographic data for trimethyltin(IV) complex showed that the tin has approximate trigonal bipyramidal geometry with the CH3 groups in the trigonal plane. The carboxylate groups bridge the adjacent tin atoms, resulting in polymeric chains. FT-IR and NMR data also support the 5-coordination geometry for the triorganotin(IV) derivatives. In the case of the diorganotin(IV) derivatives a six-coordinate geometry at the tin atom is proposed from spectroscopic data. The Me-Sn-Me bond angle in complexes 1 and 4 was determined from the (2)J[(119)Sn-(1)H] value as 138.4° and 111° that falls in the range of 5-coordinated trigonal bipyramidal and 6-coordinated octahedral geometries, respectively. The synthesized compounds were screened for their biological activities including antibacterial, antifungal and cytotoxicity. The compounds 4-6 exhibit excellent antibacterial, antifungal and cytotoxic activities. The cytotoxicity data reveals that the HL and 1-3 are almost non-toxic and exhibited LD50 values in the range 73.45-675.1µg/mL while 4-6 are found to be cytotoxic to mildly cytotoxic with LD50 values in the range 6.43-13.49µg/mL. The compound interacts with DNA via intercalation of aromatic ring into the base pairs of DNA resulting in hypochromism and minor red shift.

Stannic chloride-para toluene sulfonic acid as a novel catalyst-co-catalyst system for the designing of hydroxyl terminated polyepichlorohydrin polymer: Synthesis and characterization.

Hydroxy terminated polyepichlorohydrin (PECH) was synthesized in good yield (85-88%) with improved functionality (2.01-2.53) and desired number average molecular weight (∼3000), using a novel catalyst-co-catalyst combination. The effect of various molar ratios (4-12) of p-toluenesulphonic acid and SnCl4 on molecular weight of PECH was investigated. Different polymerization conditions like temperature, time and monomer addition rates were found to have pronounced effect on molecular weight, polydispersity and functionality of the products. The molecular weight distribution and polydispersity of the synthesized polymers were determined by Gel permeation chromatography (GPC). Absolute value of Number average molecular weight (Mn) was established with vapor pressure osmometry and structural elucidations were carried out by FT-IR and NMR spectroscopic techniques. Terminal Hydroxyl groups were quantified by acetylation method and functionality was derived from hydroxyl value and Mn.

Synthesis, spectroscopic characterization, biological screenings, DNA binding study and POM analyses of transition metal carboxylates.

This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

Synthesis, spectroscopic characterization and in vitro antimicrobial, anticancer and antileishmanial activities as well interaction with Salmon sperm DNA of newly synthesized carboxylic acid derivative, 4-(4-methoxy-2-nitrophenylamino)-4-oxobutanoic acid.

This paper stresses on the synthesis, characterization of novel carboxylic acid derivative and its application in pharmaceutics. Carboxylic acid derivatives have a growing importance in medicine, particularly in oncology. A novel carboxylic acid, 4-(4-methoxy-2-nitrophenylamino)-4-oxobutanoic acid, was synthesized and characterized by elemental analysis, FT-IR, NMR ((1)H, and (13)C), mass spectrometry and single crystal X-ray structural analysis. The structure of the title compound, C11H12N2O6, shows the molecules dimerised by short intramolecular OH⋯O hydrogen bonds. The compound was screened for in vitro antimicrobial, anticancer, and antileishmanial activities as well as interaction with SS-DNA. The compound was also checked for in vitro anticancer activity against BHK-21, H-157 and HCEC cell lines, and showed significant anticancer activity. The compound was almost non-toxic towards human corneal epithelial cells (HCEC) and did not show more than 7.4% antiproliferative activity when used at the 2.0µg/mL end concentration. It was also tested for antileishmanial activity against the promastigote form of leishmania major and obtained attractive result. DNA interaction study exposes that the binding mode of the compound with SS-DNA is an intercalative as it results in hypochromism along with minor red shift. A new and efficient strategy to identify pharmacophores sites in carboxylic acid derivative for antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.

Synthesis, spectroscopic characterization, crystal structure, DNA interaction study and invitro biological screenings of 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid.

The titled compound, 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid was synthesized and characterized by various techniques like elemental analyses, FT-IR, NMR ((1)H, and (13)C) and single crystal X-ray structural analysis. The appearance of the OH peak of the carboxylic acid in the FT-IR and NMR spectra conform the formation of the compound. A good agreement was found between the calculated values of C, H, N and found values in elemental analysis that show the purity of the compound. Protons H2 and H3 are in cis conformation with each other as conformed both from (1)H NMR as well as from single crystal X-ray analysis. The molecular structure of the title compound, C10H10NO3Cl, is stabilized by short intramolecular OH---O hydrogen bonds within the molecule. In the crystal structure, intermolecular NH---O hydrogen bonds link molecules into zigzag chains resulting in a dendrimer like structure. The title compound was screened for biological activities like interaction with DNA, cytotoxicity, antitumor and antioxidant activities. DNA interaction study reveals that the binding mode of interaction of the compound with SS-DNA is intercalative as it results in hypochromism along with significant red shift of 5 nm. It was also found to be effective antioxidant of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and show almost comparable antioxidant activity to that of the standard and known antioxidant, ascorbic acid, at higher concentration. The antitumor activity data of the compound shows that it can be used as potent antitumor agent.

Potentially bioactive organotin(IV) compounds: synthesis, characterization, in vitro bioactivities and interaction with SS-DNA.

Fourteen new organotin(IV) complexes with general formula R2SnL2 or R3SnL where R = CH3, C2H5, C4H9, C6H5, C6H11, CH2-C6H5, C(CH3)3, C8H17 and L = N-[(2-methoxyphenyl)]-4-oxo-4-[oxy]butanamide were synthesized and characterized by elemental analyses, FT-IR, NMR ((1)H, (13)C and (119)Sn), mass spectrometry and single crystal X-ray structural analysis. Crystallographic data for four triorganotin(IV) complexes (R3SnL, R = CH3, C2H5, C4H9, CH2-C6H5) showed the tin has approximate trigonal bipyramidal geometry with the R groups in the trigonal plane. The carboxylate groups of ligands L bridge adjacent tin atoms, resulting in polymeric chains. In case of the diorganotin(IV) derivatives a six-coordinate geometry at the tin atom is proposed from spectroscopic evidence. The Me-Sn-Me bond angle in complex 7 was determined from the (2)J[(119)Sn-(1)H] value as 166.3° that falls in the range of six-coordinate geometry. The ligand and its complexes (1-14) were screened for their antimicrobial, antitumor, cytotoxic and antileishmanial activities and found to be biologically active. The ligand and its complexes bind to DNA via intercalative interactions resulting in hypochromism and minor bathochromic shifts as confirmed by UV-visible spectroscopy. Based on in vitro studies such as the potato disc method, the synthesized compounds were found to possess significant antitumor activity. Also, from cytotoxicity and DNA interaction studies, these compounds can also be used for the prevention and treatment of cancer. Gel electrophoresis assay was used to investigate the damage to double stranded super coiled plasmid pBR322 DNA by the synthesized compounds and compounds 1 and 7 were found to cause the maximum damage. All the synthesized compounds exhibit strong antileishmanial activity that was even higher than that of Amphotericin B, with significant cytotoxicity. This study, therefore, demonstrated the potential use of these compounds as source of novel agents for the treatment of leishmaniasis.

Potential bioactive Schiff base compounds: synthesis, characterization, X-ray structures, biological screenings and interaction with Salmon sperm DNA.

Three Schiff base compounds ofN'-substituted benzohydrazide and sulfonohydrazide derivatives: N'-(2-hydroxy-3-methoxybenzylidene)-4-tert-butyl- benzohydrazide (1), N'-(5-bromo-2-hydroxybenzylidene)-4-tert-butylbenzohydrazide (2) and N'-(2-hydroxy-3-methoxybenzylidene)-4-methylbenzenesulfonohydrazide (3) were synthesized and characterized by elemental analysis, FT-IR, (1)H, (13)C NMR spectroscopy and single crystal analysis. The title compounds have been screened for their biological activities including, antibacterial, antifungal, antioxidant, cytotoxic, enzymatic activities as well as interaction with SS-DNA which showed remarkable activities in each area of research. The DNA binding of the compounds 1-3 with SS-DNA has been carried out with absorption spectroscopy, which reveals the binding propensity towards SS-DNA via intercalation mode of interaction. The intercalative mode of interaction is also supported by viscometric results. The synthesized compounds were also found to be effective against alkaline phosphatase enzyme. They also show significant to good antimicrobial activity against six bacterial and five fungal strains. The MIC (minimum inhibitory concentration) for antibacterial activity ranges from 1.95-500 µg/mL. Compounds 1-3 show cytotoxic activity comparable to the control. At higher conc. (100 µg/L) compound 3 shows 100% activity means that it has killed all brine shrimps. They were also found to be effective antioxidant of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and show almost comparable antioxidant activity to that of the standard and known antioxidant, ascorbic acid.

Drug-DNA interactions and their study by UV-Visible, fluorescence spectroscopies and cyclic voltametry.

The present paper review the drug-DNA interactions, their types and applications of experimental techniques used to study interactions between DNA and small ligand molecules that are potentially of pharmaceutical interest. DNA has been known to be the cellular target for many cytotoxic anticancer agents for several decades. Understanding how drug molecules interact with DNA has become an active research area at the interface between chemistry, molecular biology and medicine. In this review article, we attempt to bring together topics that cover the breadth of this large area of research. The interaction of drugs with DNA is a significant feature in pharmacology and plays a vital role in the determination of the mechanisms of drug action and designing of more efficient and specifically targeted drugs with lesser side effects. Several instrumental techniques are used to study such interactions. In the present review, we will discuss UV-Visible spectroscopy, fluorescence spectroscopy and cyclic voltammetry. The applications of spectroscopic techniques are reviewed and we have discussed the type of information (qualitative or quantitative) that can be obtained from the use of each technique. Not only have novel techniques been applied to study drug-DNA interactions but such interactions may also be the basis for the development of new assays. The interaction between DNA and drugs can cause chemical and conformational modifications and, thus, variation of the electrochemical properties of nucleobases.