Ashraf Mashrai

Synthesis and anti-tumor evaluation of B-ring substituted steroidal pyrazoline derivatives

The synthesis and anti-tumor activity screening of new steroidal derivatives (4-18) containing pharmacologically attractive pyrazoline moieties are performed. During in vitro anticancer evaluation, the newly synthesized compounds displayed moderate to good cytotoxicity on cervical and leukemia cancer cell lines. In addition these compounds were found to be nontoxic to normal cell (PBMCs) (IC50>50 μM). The structure-activity relationship is also discussed. The most effective anticancer compound 9 was found to be active with IC50 value of 10.6 μM. It demonstrated significant antiproliferative influence on Jurkat cell lines. The morphological changes and growth characteristics of HeLa cells treated with compound 4 were analyzed by means of SEM.

Synthesis and characterization of steroidal heterocyclic compounds, DNA condensation and molecular docking studies and their in vitro anticancer and acetylcholinesterase inhibition activities

A facile, convenient and efficient approach for the synthesis of a new series of steroidal heterocyclic compounds (4–12) by reacting a mixture of compounds (1e–3e) with o-aminothiophenol/o-aminophenol/o-phenylenediamine is reported. The structural assignment of products is confirmed on the basis of IR, 1H NMR, 13C NMR, MS and analytical data. The compounds obey the Lipinskis ‘Rule of Five’ analysis based on computational prediction and pharmacokinetic properties. The anticancer activity has been tested in vitro against three cancer cell lines Hep3B (human hepatocellular carcinoma), MCF7 (human breast adenocarcinoma), HeLa (human cervical carcinoma) and one non-cancer normal cell i.e. PBMCs (peripheral blood mononuclear cell) by MTT assay. In addition, the synthesized compounds are also tested for their in vitro antioxidant activity by various reported methods in which compounds 10–12 exhibited good antioxidant activity. Nonenzymatic degradation of DNA has been investigated. The acetylcholinesterase (AChE) inhibitor activities of the steroidal derivatives are also evaluated using Ellmans method. Moreover, the application of compound 6 as a DNA gene transporter is evaluated by DNA condensation and ascertained by employing TEM and AFM, which illustrate that the compound 6 induces the condensation of CT-DNA. Molecular docking studies further characterize the interaction of the synthesized compounds with DNA.

Synthesis, crystal structure, Hirshfeld surfaces, and thermal, mechanical and dielectrical properties of cholest-5-ene

Abstract The title compound derived from 3β-chlorocholest-5-ene has been synthesized and characterized successfully. A single crystal X-ray investigation of the compound revealed that the van der Waals interactions play a key role in the formation of the elementary structure. Hirshfeld surface analysis was used to visualize the fidelity of the crystal structure. This method permitted the identification of individual types of intermolecular contacts and their impact on crystal packing. Molecules are linked by a combination of C–H⋯H and C⋯H contacts, which have clear signatures in the fingerprint plots. The absorption spectrum exhibited a strong absorption band of approximately 246 nm, and the fluorescence spectrum of the compound showed one broad peak at 367 nm. Thermal studies established that the compound undergoes no phase transition and is stable up to 200 °C. The hardness of the grown crystal increases as the load increases. The electric permittivity of cholest-5-ene decreases with increasing frequency and becomes almost constant at high frequencies.

N1-[(1H-Imidazol-2-yl)methyl­idene]-N4-phenyl­benzene-1,4-di­amine

The title compound, C16H14N4, is non-planar with dihedral angles between the planes of the imidazole and phenylenediamine rings of 30.66 (4)° and between the planes of the phenylenediamine and N-phenyl rings of 56.63 (7)°. In the crystal, molecules are connected by N—H⋯N hydrogen bonds, generating a chain extending along the b-axis direction. The crystal structure is also stabilized by C—H⋯π interactions between N-phenyl and imidazole rings and slipped π–π stacking interactions between imidazole rings [centroid–centroid distance = 3.516 (4) Å] giving an overall two-dimensional layered structure lying parallel to (010).

Strategies for the Synthesis of Thiazolidinone Heterocycles

Thiazolidinones is the special class of heterocyclic compounds with a broad spectrum of biological activities such as anti-inflammatory, antiproliferative, antihistaminic, anti-HIV, hypnotic, anaesthetic, antifungal, anthelmintic and antiviral agents as well as CNS stimulants. Therefore researchers have synthesized these condensed heterocycles through different complex pathways as target structures for biological studies. This review focuses on the various strategies followed for the convenient synthesis of thiazolidinone based heterocyclic derivatives. The steps included condensation followed by cyclization of Schiff’s bases, either in a step-wise manner or in one pot under different conditions. Mercaptoacetic acid, thiolactic acid, chloroacetyl chloride, potassium thiocyanate, ethylchloro acetate and ammonium thiocyanate are the most common reagents used for the synthesis thiazolidinone appended on different heterocyclic skeletons.

Crystal structure of N (1)-phenyl-N (4)-[(quinolin-2-yl)methyl-idene]benzene-1,4-di-amine.

In the title compound, C22H17N3, the dihedral angles between the central benzene ring and the terminal phenyl ring and quinoline ring system (r.m.s. deviation = 0.027 Å) are 44.72 (7) and 9.02 (4)°, respectively, and the bond-angle sum at the amine N atom is 359.9°. In the crystal, the N—H group is not involved in hydrogen bonding and the molecules are linked by weak C—H⋯π interactions, generating [010] chains.

DNA binding, artificial nuclease activity and cytotoxic studies of newly synthesized steroidal pyrimidines

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 Kb; 2.31×103M-1, 1.93×103M-1 and 2.05×103M-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.

Cytotoxic Evaluation and DNA Binding Ability of Catalytically SynthesizedNew Steroidal Lactones

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.

2,2,6,6-Tetra­bromo-3,4,4,5-tetra­meth­oxy­cyclo­hexa­none

In the title compound, C10H14Br4O5, synthesized from the methoxy Schiff base N-(pyridin-2-ylmethyl)methoxyaniline and molecular bromine, the cyclohexanone ring has a chair conformation with one of the four methoxy groups equatorially orientated with respect to the carbonyl group and the others axially orientated. The C—Br bond lengthsvary from 1.942 (4) to1.964 (4) Å. In the crystal, weak C—H⋯Ocarbonyl hydrogen-bonding interactions generate chains extending along the b-axis direction. Also present in the structure are two short intermolecular Br⋯Omethoxy interactions [3.020 (3) and 3.073 (4) Å].

6-Hy­droxy­imino-5α-cholestane

The title compound, C27H47NO, is a steroid derivative composed of a saturated carbon fused-ring framework with an alkyl side chain. Ring bond lengths have normal values with an average of 1.533 (2) Å, while the cholestane side chain shows an average bond length of 1.533 (2) Å. The three cyclohexane rings adopt chair conformations or close to chair conformations while the cyclopentane ring is twisted. The cholesterol side-chain is fully extended with a gauche–trans conformation of the terminal methyl groups. There are eight chiral centres in the molecule; the absolute configuration of these sites was determined from the structure presented. There are two molecules in the asymmetric unit; in one, the alkyl chain is disordered over two sets of sites [occupancy ratios of 0.50:0.50 and 0.67:0.33].