Muhammad Sirajuddin

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.

Synthesis, characterization, biological screenings and interaction with calf thymus DNA of a novel azomethine 3-((3,5-dimethylphenylimino)methyl)benzene-1,2-diol.

The novel azomethine, 3-((3,5-dimethylphenylimino)methyl)benzene-1,2-diol (HL) was synthesized and characterized by elemental analysis, FT-IR, (1)H, (13)C NMR spectroscopy and single crystal analysis. The title compound has been screened for its biological activities including enzymatic study, antibacterial, antifungal, cytotoxicity, antioxidant and interaction with CTDNA, and showed remarkable activities in each area of research. The titled compound interacts with DNA via two binding modes: intercalation and groove binding. In intercalation the compound inserts itself into the base pairs of DNA and the compound-DNA complex is stabilized by π-π stacking. Interaction via groove binding may be due to hydrogen bonding to bases, typically to N3 of adenine and O2 of thymine. The synthesized compound was also found to be an effective antioxidant of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and gives percent inhibition (%I) of 90.7 at a concentration level of 31.3μg/mL.

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.

Biological screening, DNA interaction studies, and catalytic activity of organotin(IV) 2-(4-ethylbenzylidene) butanoic acid derivatives: synthesis, spectroscopic characterization, and X-ray structure

A series of organotin(IV) carboxylates, [Me2SnL2] (1), [Bu2SnL2] (2), [Oct2SnL2] (3), [Me3SnL] (4), and [Ph3SnL] (5), where L = 2-(4-ethylbenzylidene) butanoic acid, have been synthesized and characterized by elemental analysis, FT-IR, and NMR (1H, 13C, and 119Sn). [Me3SnL] (4) was analyzed by single crystal X-ray analysis which showed polymeric structure with distorted trigonal bipyramidal geometry. The complexes were screened for biological activities including antibacterial, antifungal, and cytotoxic activities. UV–vis absorption studies of HL, 1 and 4 with SS-DNA revealed groove binding as well as intercalation, which may be due to the presence of planar phenyl groups that facilitate interaction with DNA. The determined intrinsic binding constants, 6.04 × 103 M−1 (HL), 9.6 × 103 M−1 (1), and 1.7 × 104 M−1 (4), showed that HL and 1 have less binding strength than 4. The catalytic activities of di- and tri-organotin(IV) complexes were assessed in transesterification of triglycerides (linseed oil) into fatty acid methyl esters (biodiesel). The tri-organotin(IV) complexes have better catalytic activity than their di-analogs. The synthesized compounds interact with SS-DNA via intercalative binding mode of interaction in which the compound insert itself into the base pair of DNA resulting in hypochromic and bathochromic shift.

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.

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, 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.

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.

Synthesis, spectral characterization and in vitro antibacterial evaluation and Petra/Osiris/Molinspiration analyses of new Palladium(II) iodide complexes with thioamides

Abstract The paper emphasizes on the synthesis of Palladium(II) iodide complexes containing based ligands. The new compounds of general formulae [Pd(L)4]I2 where L = Thiourea (Tu), Methylthiourea (Metu), Dimethylthiourea (Dmtu), Tetramethylthiourea (Tmtu), Imidazolidine-2-thione (Imt), Mercaptopyridine (Mpy), Mercaptopyrimidine (Mpm), and Thionicotinamide (Tna) were prepared simply by reacting K2[PdCl4] with the corresponding thioamides in 1:2 M ratio and then with 2 equivalents Potassium iodide. The complexes were characterized by elemental analysis and spectroscopic techniques (IR, 1H and 13C NMR). All the synthesized complexes were screened for antibacterial activity and some of compounds have shown good activities against both gram positive and gram negative bacteria. POM analyses reveal that the compounds are only slightly toxic and present a potential for antibacterial activity. Moreover, they have 16–23% drug score which is an important parameter for the compound possessing the drug properties.

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.