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The new steroidal pyrimidine derivatives (4-6) were synthesized by the reaction of steroidal thiosemicarbazones with (2-methyl) diethyl malonate in absolute ethanol. After characterization by spectral and analytical data, the DNA interaction studies of compounds (4-6) were carried out by UV-vis, fluorescence spectroscopy, hydrodynamic measurements, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with K-b; 2.31 x 10(3) M-1, 1.93 x 10(3) M-1 and 2.05 x 10(3) M-1, respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis demonstrated that compound 4 showed a strong interaction during the concentration dependent cleavage activity with pBR322 DNA. The molecular docking study suggested the intercalation of steroidal pyrimidine moiety in the minor groove of DNA. During in vitro cytotoxicity, compounds (4-6) revealed potential toxicity against the different human cancer cells (MTT assay). During DAPI staining, the nuclear fragmentations on cells occurred after treatment with compounds 4 and 5. Western blotting analysis clearly indicates that compound 4 causes apoptosis in MCF-7 cancer cells. The results revealed that compound 4 has better prospectus to act as a cancer chemotherapeutic candidate, which warrants further in vivo anticancer investigations. (C) 2017 Published by Elsevier B.V.

New steroidal imidazolidinthione derivatives (4–6) were synthesized from steroidal thiosemicarbazones and dichloroethane. The synthesized compounds were characterized using spectral data analysis. Theoretical DFT involving B3LYP/6-31G∗∗ level of theory was employed to gain insights into the molecular structure of the target compounds. MEPS and FMO analysis were carried out. HOMO-LUMO energy gap was determined which helped to evaluate various global descriptors like hardness, chemical potential, electronegativity, nucleophilicity and electrophilicity index, etc. The calculated properties established that the synthesized products are more or less similar in their reactivity behaviour. To explore their biological potential, interaction studies of compounds (4–6) with DNA were carried out using various biophysical techniques. The compounds bind DNA preferentially through electrostatic and hydrophobic interactions with Kb of 3.21 × 103 M−1, 2.79 × 103 M−1 and 2.26 × 103 M−1, respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis of compound 4 demonstrated strong interaction during the concentration dependent cleavage activity with pBR322 DNA. It was observed that these steroidal imidazolidinthiones are minor groove binders of DNA which was validated using molecular docking studies. An in vitro cytotoxicity screening using MTT assay revealed that the compounds (4–6) exhibit potential toxicity against different human cancer cells. Highest antiproliferative effect was observed on HeLa cells by compound 4. The results suggested that compounds 4–6 cause apoptotic cell death by cleaving apoptotic protein caspase-3 and suppress anti-apoptotic protein Bcl-2 in HeLa cancer cells.

In the present study steroidal derivatives, 3β-[5′-mercapto-1′,3′,4′-oxadiazole-2-yl]methoxy cholest-5-ene 2 , 3β-[2′,5′-dimethylpyrrole-1-yl]aminocarbonylmethoxycholest-5-ene 3 and 3 β-[3′,5′-dimethyl pyrazole-1-yl]carbonylmethoxycholest-5-ene 4 have been synthesized from cholest-5-en-3β- O -acetyl hydrazide 1 using CS 2 /KOH, acetonyl acetone and acetyl acetone, respectively as reagents and are characterized by IR, 1 H NMR, 13 C NMR, MS and elemental analysis. Compounds 2 – 4 were also evaluated for anticancer activity against human leukemia cell line (HL-60) by MTT assay and compound 4 displayed the promising behavior by showing better anticancer activity.

Herein we report synthesis of new steroidal oxadiazinanones from steroidal ketones. After characterization by spectral and analytical data, the interaction studies of compounds (4–6) with DNA were carried out by UV–vis, fluorescence spectroscopy and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 1.8 × 104 M−1, 2.2 × 104 M−1 and 2.6 × 104 M−1, respectively, indicating the higher binding affinity of compound 6 towards DNA. Gel electrophoresis showed the concentration dependent cleavage activity of compound 6 alone or in presence of Cu (II) causes the nicking of supercoiled pBR322 and it seems to follow the mechanistic pathway involving generation of hydroxyl radicals that are responsible for initiating DNA strand scission. Molecular simulations suggest that compounds binds through minor groove of DNA. MTT assay depicted promising anticancer activity of compound 5 and 6 particularly against HL-60 and MCF-7. The apoptotic degradation of DNA was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). The results revealed that compound 6 has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.

A new series of steroidal dihydrocarbothioic acid amido pyrazole analogues were synthesized, and after characterization, evaluation for cytotoxicity, comet assay and western blotting was carried out. The synthesis of these analogues is convenient and involves two steps, i.e. aldol condensation as first step followed by nucleophilic addition of thiosemicarbazide across α, β-unsaturated carbonyl as a later step. Quantitative yields of more than 80 % are obtained in both the steps. After characterization by IR, (1)H NMR, (13)C NMR, MS and analytical data, all the compounds of both series were tested for cytotoxic activity against a panel of different human cancer cell lines by MTT assay, during which compound 3e, 3f, 4e, 4f and 4h are very potent especially against HepG2 and MCF-7 cancer cell lines. Cell cycle analysis depicted the cell death in S-phase while as annexin V-FITC/PI analysis showed that compounds effectively induce apoptosis. Apoptotic degradation of DNA of MCF-7 cells in the presence of different steroidal derivatives was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). In western blotting analysis, the relative expressions of relevant apoptotic markers depicted an apoptosis by steroidal dihydropyrazole in MCF-7 cancer cells.

In an attempt to find a new class of cytotoxic agents, a series of fused steroidal derivatives containing lactone moiety were prepared via Michael addition reaction of α, β-unsaturated steroidal ketones with ethyl chloroacetate in basic medium. The characterization of novel compounds was accomplished by spectroscopic techniques such as IR, 1H NMR, 13C NMR, Mass spectrometry and elemental analysis. The compounds were screened for in vitro cytotoxicity against some particular human cancer cell lines using the MTT assay during which the compound 4 and 5 depicted potential anticancer behavior after showing IC50=19.41 μmol L−1 and 19.27 μmol L−1 against HeLa and MCF-7 cell line, respectively. The Gel electrophoresis demonstrated that steroidal lactone showed strong interaction during the concentration dependent cleavage activity with pBR322 DNA. The molecular docking study suggested the non-covalent bonding of steroidal lactones in minor groove of DNA. The results revealed that the synthesized compounds have better prospectus to act as cancer chemotherapeutic candidates which warrants further in vivo anticancer investigations.

A series of new 5α-cholestano [5,6-b] benzothiazines ( 4 – 6 ) has been synthesized by the reaction of 5α-cholestan-6-one ( 1 – 3 ) with 2-aminothiophenol in the presence of iodine. The structures of newly synthesized compounds have been established on the basis of spectral and analytical data. Compounds ( 1 – 6 ) were screened for in vitro anticancer activity against the human cancer cell lines; SW480 (colon adenocarcinoma cells), A549 (lung carcinoma cells), HepG2 (hepatic carcinoma cells) and HeLa (cervical cancer cells) using MTT assay during which the products ( 4 – 6 ) showed marked increase in anticancer activity and in particular, compound 6 showed IC 50 = 13.73 μmol L −1 against HeLa cells, being more effective than Doxorubicin against the same cells. Compounds 4 and 6 also showed minimum IC 50 of 15.83 μmol L −1 and 16.89 μmol L −1 against HepG2 and A549 cells, respectively. Compounds ( 1 – 6 ) were also tested for in vitro antimicrobial activity against different bacterial as well as fungal strains during which newly synthesized compounds ( 4 – 6 ) were found more potent than starting compounds ( 1 – 3 ). Compound 4 was found to be more potent than the reference drug, Chloramphenicol, in the case of Escherichia coli while compound 5 was found almost equally potential antifungal agent against P. marneffei in comparison with the reference drug, Nystatin.

A new series of steroidal pyrimidines (7–9) has been synthesized by reacting steroidal thiosemicarbazones (4–6) with ethyl cyanoacetate. The compounds were characterized by IR, 1H NMR, 13C NMR, MS and analytical data. The interaction studies of compounds 7–9 with DNA were carried out by UV–vis and luminescence spectroscopy. Compounds (7–9) bind to DNA preferentially through electrostatic and hydrophobic interactions, with Kb values found to be 6.56 × 103 M−1, 1.54 × 104 M−1 and 9.34 × 103 M−1, respectively, indicating the higher binding affinity of compound 8 towards DNA. Gel electrophoresis pattern demonstrated that compound 8 shows strong interaction with DNA and that, during its cleavage activity with pBR322 DNA, it seems to follow the mechanistic pathway involving the generation of singlet oxygen and a superoxide anion, which are responsible for initiating DNA strand scission. The docking study suggested that the intercalation of compounds in between the nucleotide base pairs is due to the presence of a pyrimidine moiety in the steroid molecule. MTT assay was carried out to check the toxicity of new compounds 7–9 against the different human cancer as well as non-cancer cell lines A545, MCF-7, HeLa, HL-60, SW480, HepG2, HT-29, A549, 184B5, MCF10A, NL-20, HPC, and HPLF. Apoptotic degradation of DNA in the presence of steroidal pyrimidines 7–9 was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay).

A series of new steroidal imidazolidine derivatives (4-6) were synthesized after reacting steroidal thiosemicarbazones with chloro ethylacetate in absolute ethanol. After characterization by spectral and analytical data, the interaction studies of compounds (4-6) with DNA were carried out by UV-vis, fluorescence spectroscopy, hydrodynamic measurements, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.63 × 10(3) M(-1), 1.81 × 10(3) M(-1) and 2.06 × 10(3) M(-1), respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis demonstrated that compound 4 showed strong interaction during the concentration dependent cleavage activity with pBR322 DNA. The molecular docking study suggested the intercalation of imidazolidine moiety of steroid derivative in minor groove of DNA. During in vitro cytotoxicity, compounds (4-6) revealed potential toxicity against the different human cancer cells (MTT assay). The uptake of compound 4 by MCF-7 and HeLa cells was studied by confocal microscopy which determined cell shrinkage and hence leading to the apoptosis. The results revealed that compound 4 has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.

A one-pot strategy for the catalytic synthesis of series of new 5α-cholestan-6-spiro-5'-phenylamino-2H-imidazo [1',2'-a] pyridines (4-14) has been investigated. The synthesized products were obtained in good yields (85-90%) and the protocol uses Multi-component Reaction (MCR) involving steroidal ketones, 2-aminopyridines, isocyanides and propylphosphonic anhydride (®T3P) as a catalyst. After characterization by spectral and analytical data, the interaction studies of compounds (4-6) with DNA were studied by UV-vis, fluorescence spectroscopy, gel electrophoresis and molecular docking. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.35×10(4), 3.71×10(4) and 3.24×10(4) M(-1), respectively, indicating the higher binding affinity of compound 5 towards DNA. Gel electrophoresis showed the concentration dependent cleavage activity of compounds 4-6 with DNA. Molecular docking studies suggested that compounds bind through minor groove to DNA. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay depicted promising anti-proliferative activity of compound 4-9 against different given cancer cells. In Western blotting, the expressions of relevant apoptotic markers depicted an apoptosis by steroidal imidazopyridines in A549 cells. Annexin V-FITC/PI staining data indicated that compounds could effectively induce apoptosis in A549 cells in a dose-dependent manner. FACS analysis shows that the compound 6 bring about cell cycle arrest at 2.62 μM concentration.

New steroidal imidazolidinone derivatives (7-9) were synthesized after reacting steroidal thiosemicarbazones with oxalyl chloride in absolute ethanol. After characterization by spectral and analytical data, the interaction studies of compounds (7-9) with DNA were carried out by UV-vis, fluorescence spectroscopy, circular dichroism, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.31 × 10(4) M(-1), 2.57 × 10(4) M(-1) and 2.16 × 10(4) M(-1), respectively indicating the higher binding affinity of compound 8 towards DNA. Gel electrophoresis demonstrated that the compounds 7-9 show strong interaction during the cleavage activity with pBR322 DNA. The docking study suggested the intercalation of imidazolidinone moiety of steroid derivative in minor groove of DNA. During in vitro cytotoxicity, compounds 7-9 revealed potential toxicity against the different human cancer cells (MTT assay). Apoptotic degradation of DNA in presence of compounds 7-9 was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). FACS analysis shows that the compound 8 bring about cell cycle arrest at 7 μM concentration.

The design and synthesis of medicinal chemotherapeutic agents of copper with 2-(benzothiazol-2-yl iminomethyl)-phenol, 2-(benzothiazol-2-yliminomethyl)-valine, cyanoaceto (2-mer- captobenzylidene)-hydrazide, 2-(phenacyl bromide)-aminothiophenol, (2-mercaptobenzaldehyde) thio- semicarbazone, N-(phenacyl bromide)-2- yliminobenzothiazole, 2-aminobenzothiazole, benzothiazol-2-yliminomethyl)-phenol and 2-[(2E¹-aminobenzylidene)- amino]-benzenethiol were synthesized. The characterization was done by FTIR, 1H and 13C NMR, MS, TGA and elemental analysis. Interaction of complexes 8 and 9 with CT DNA was done by using UV-vis and fluorescence spectroscopy depicting the hyperchromic behaviour of complexes. The intrinsic binding constants (Kb) for complex 8 and 9 were 2.35 × 103 M-1 and 2.12 × 103 M-1. The cleavage studies of complex 8 and 9 were done with pBR322 plasmid showing the potential cleaving ability of the complexes at very low concentration. The gel electrophoresis pattern also demonstrated that the complex 8 alone or in presence of Cu (II) causes the nicking of supercoiled pBR322 and it seems to follow the mechanistic pathway involving generation of hydroxyl radicals that are responsible for initiating DNA strand scission. The molecular docking studies showed the minor groove binding behaviour of the complexes 8 and 9 with DNA. During the MTT assay against different cancer cell lines like SW480, HepG2, HT29 and HL60, all the complexes showed potential cytotoxic behaviour by giving effective IC50 close to Cisplatin. The bioactivity score and PASS analysis also depicted the drug like nature of the complexes. During the comet assay, apoptotic degradation of DNA in the presence of complex 8 and 9 was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining.

New steroidal imidazolidine derivatives (7-9) were synthesized by reacting steroidal thiosemicarbazones (4-6) with ethyl-2-chloroacetate in absolute ethanol. After characterization by spectral and analytical data, the interaction studies of compounds (7-9) with DNA were carried out by UV-vis, luminescence spectroscopy, circular dichroism and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.07 × 104 M-1, 2.1 × 104 M–1 and 1.9 × 104 M–1, respectively indicating the higher binding affinity of compound 8 towards DNA. Gel electrophoresis demonstrated that the compound 8 show strong interaction with DNA and during its cleavage activity with pBR322 DNA, it seems to follow the mechanistic pathway, involving singlet oxygen and superoxide anion to generate ROS responsible for initiating DNA strand scission. The docking study suggested the intercalation of imidazolidine moiety of steroid derivative in minor groove of DNA. In MTT assay, compounds 7-9 revealed potential toxicity against different human cancer cells especially compound 8 against A549 cells. Genotoxicity of compounds (7-9) was checked by comet assay. In western blotting, the expressions of relevant apoptotic markers depicted an apoptosis by steroidal imidazolidines in A549 cells.

Steroid based cancer chemotherapeutic agents of the type 2′-amino-3′-cyanocholest-6-eno[5,7-de]4H-pyrans ( 1c – 3c ) have been synthesized and characterized by the various spectroscopic and analytical techniques. The DNA binding studies of compounds ( 1c – 3c ) with CT DNA were carried out by UV–vis and fluorescence spectroscopy and gel electrophoresis. The compounds ( 1c – 3c ) bind to DNA preferentially through electrostatic and hydrophobic interactions with K b values found to be 5.4 × 10 3 , 2.3 × 10 3 M −1 and 1.97 × 10 3 M −1 , respectively indicating the higher binding affinity of compound ( 1c ) towards DNA. The molecular docking study suggested that the electrostatic interaction of compounds ( 1c – 3c ) in between the nucleotide base pairs is due to the presence of pyran moiety in steroid molecule. All the compounds ( 1c – 3c ) cleave supercoiled pBR322 DNA via hydrolytic pathway, as validated by T4 DNA ligase assay. The compounds ( 1c – 3c ) were screened for in vitro cytotoxicity against the cancer and non-cancer cells SW480, A549, HepG2, HeLa, MCF-7, HL-60, DU-145, NL-20, HPC and HPLF by MTT assay. The compounds ( 1c – 3c ) were tested for genotoxicity (comet assay) involving apoptotic degradation of DNA and was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining. The results revealed that compound ( 1c ) has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.