Sana Aslam

Synthesis and antioxidant studies of novel N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H) -yl)acetamides

Two new series of twenty-two N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides were synthesized by synergism of the dihydropyrazolo[4,3-c][1,2]benzothiazine 5,5-dioxide moiety with side chain of carboxamides. The routes of formation for these products have been discussed. All the compounds were characterized by NMR, mass and elemental analysis. Structures of compounds 6d and 6l have been elucidated by X-ray crystallography. The synthesized compounds were screened to the preliminary evaluation for their anti-oxidant activities and most of the compounds were found to possess moderate to significant radical scavenging activity. Furthermore, these compounds could be useful as a template for future development through modification or derivatization to design more potent biologically active compounds.Graphical Abstract[Two series of novel carboxamides based upon pyrazolobenzothiazine ring system have been synthesized and evaluated for antioxidant activity. Many compounds were found to be good scavengers of superoxide anion radical. Moreover, the compounds may also possess the bioactivities of parent ring system and thus, are useful as template for further development of new bioactive molecules.]

Novel structural hybrids of pyrazolobenzothiazines with benzimidazoles as cholinesterase inhibitors.

Two series of novel pyrazolobenzothiazine-based hybrid compounds were efficiently synthesized starting from saccharin sodium salt. Pyrazolo[4,3-c][1,2]benzothiazine scaffolds were N-arylated by using p-fluorobenzaldehyde, followed by the incorporation of a benzimidazole or similar ring systems by treatment with arylenediamines. These phenylene-connected hybrid compounds were investigated as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Compounds 12d and 12k were the most potent AChE inhibitors with IC50 values of 11 and 13 nM, respectively, while 6j (IC50 = 17 nM) proved to be the most active inhibitor against BuChE with remarkable selectivity for BuChE over AChE. Molecular docking studies were also performed on human AChE and BuChE to suggest possible binding modes in which the inhibitors extended structure is accommodated along the active site gorge of both enzymes.

Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides.

Two series of fifteen N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides were screened for anti-HIV-1 activity and cytotoxicity. The compounds 6a, 6d, 6e, 6g and 6i from the series 6a-i of benzylamides and 7a, 7b, 7c, 7d and 7e from the series 7a-f of anilides were identified as effective anti-HIV-1 agents with EC50 values <20μM. Among these compounds that displayed anti-HIV-1 activity, 6a, 6e, 6g and 6i showed no toxicity in human PBM, CEM and Vero cells, with the exception of 6a which displayed toxicity in Vero cells. Molecular docking of these compounds provided insight into the molecular mechanism and it was found that 6e, 6g and 6i bound deeply in the NNRTI binding pocket of the HIV-1 reverse transcriptase, using RT-bound nevirapine X-ray data and molecular docking for validation, showing the potential of these new structures as inhibitors of this viral enzyme.

3-(3-Chloro-benzo-yl)-4-hydr-oxy-2H-1,2-benzothia-zine 1,1-dioxide.

In the title compound, C15H10ClNO4S, the heterocyclic thiazine ring adopts a half-chair conformation with the S and N atoms displaced by 0.476 (5) and 0.227 (5) Å, respectively, on opposite sides of the mean plane formed by the remaining ring atoms. The structure is stabilized by intermolecular N—H⋯O and C—H⋯O hydrogen bonds. In addition, intramolecular O—H⋯O and C—H⋯N interactions are also present.

Novel Armed Pyrazolobenzothiazine Derivatives: Synthesis, X-Ray Crystal Structure and POM analyses of Biological Activity Against Drug Resistant Clinical Isolate of Staphylococcus aureus

Novel structural hybrids of pyrazolobenzothiazine and triazole ring systems have been prepared to observe a synergistic effect of the two ring systems. The methodology involves condensation of pyrazolobenzothiazine rings with methyl chloroacetate, followed by hydrazide formation. The hydrazides were converted to triazoles through the formation of intermediate potassium salts of dithiocarbazate. The final compounds as well as intermediates were screened for their antibacterial activity against a multidrug resistant strain of Staphylococcus aureus. It was interesting to observe that dithiocarbazates (7a, 7b) and target triazoles (8a, 8b) exhibited antibacterial activity.

Structural, Morphological, and Magnetic Characterization of Sol-Gel Synthesized MnCuZn Ferrites

Manganese copper ferrites belong to a family of ferrites with specific importance due to their high permeability values and low losses at low frequencies. In this paper, a series of ferrite samples has been synthesized using a novel and low cost sol-gel autocombustion route in order to systematically investigate the structural, compositional, morphological, and magnetic properties when zinc is substituted by copper in the series. X-ray diffraction reveals that all the samples have characteristic cubic spinel structure. The effect of zinc substitution at the copper site on the chemical bonding of the ferrite samples was investigated by Fourier transform infrared spectroscopy. Energy dispersive X-ray analysis was performed to determine the homogeneity and stoichiometric composition of elements present in the samples. Nanosized, uniformly shaped grains were evident from the images obtained using a scanning electron microscopy, which indirectly confirms the significance of the autocombustion synthesis technique employed in this paper. Magnetic properties determined using a vibrating sample magnetometer exhibited that zinc substitution could enhance the saturation magnetization of the samples, attributed to the substitution of a paramagnetic element (zinc) by a diamagnetic one (copper).

2-(3,4-Dimethyl-5,5-dioxo-2H,4H-pyrazolo­[4,3-c][1,2]benzothia­zin-2-yl)-N-(2-fluoro­benz­yl)acetamide

In the title molecule, C20H19FN4O3S, the heterocyclic thiazine ring adopts a half-chair conformation with the S atom displaced by 0.668 (4) Å from the mean plane formed by the remaining ring atoms. The mean planes of the benzene and pyrazole rings are inclined with respect to each other at a dihedral angle of 17.4 (3)°. The acetamide chain (O/N/C/C/C) linking the pyrazole and 2-fluorobenzyl rings is essentially planar (r.m.s. deviation = 0.030 Å) and forms dihedral angles with the mean planes of these rings of 78.8 (2) and 78.89 (14)°, respectively. The crystal structure is stabilized by N—H⋯O and C—H⋯O hydrogen-bonding interactions, resulting in a six-membered ring with an R 2 1(6) motif, while C—H⋯O and C—H⋯F hydrogen-bonding interactions result in chains of molecules lying along the c axis in a zigzag fashion.

3,4-Dimethyl-2-(2-oxo-2-phenyl-eth-yl)-2H,4H-pyrazolo-[4,3-c][1,2]benzothia-zine-5,5-dione.

In the title molecule, C19H17N3O3S, the heterocyclic thiazine ring adopts a half-chair conformation with the S and N atoms displaced by 0.530 (5) and 0.229 (6) Å, respectively, on opposite sides of the mean plane formed by the remaining ring atoms. The ethanone group lies at an angle of 3.8 (3)° with respect to the benzene ring, which lies almost perendicular to the pyrazole ring, with a dihedral between the two planes of 89.22 (11)°. Weak intermolecular C—H⋯O hydrogen-bonding interactions are present.

2-(3,4-Dimethyl-5,5-dioxo-2H,4H-pyrazolo-[4,3-c][1,2]benzothia-zin-2-yl)acetic acid.

In the title molecule, C13H13N3O4S, the heterocyclic thiazine ring adopts a half-chair conformation in which the S and an adjacent C atom are displaced by 0.919 (3) and 0.300 (4) Å, respectively, on the same side of the mean plane formed by the remaining ring atoms. The mean planes of the benzene and pyrazole rings are inclined at a dihedral angle of 18.32 (12)° with respect to each other. The acetate group is oriented at 80.75 (8)° with respect to the pyrazole ring. The crystal structure is stabilized by O—H⋯N and C—H⋯O hydrogen bonds, resulting in fused eight- and seven-membered rings with R 2 2(8) and R 2 2(7) graph-set motifs, respectively.

Benzimidazole Ring System as a Privileged Template for Anticancer Agents

Cancer still remains a continued threat for human race in the 21st century. It is the major cause of human casualties globally and is thus, a hot topic of research in medicinal laboratories. Scientists are striving to find selective anticancer agents having low toxicity for normal human cells. Heterocyclic ring systems play key role as templates/pharmacophores for various drugs, and benzimidazole ring is especially important for its anticancer derivatives. In this review article, we have focused on the structural features of anticancer derivatives based on benzimidazole ring system. It highlights various benzimidazole-based anticancer compounds which have been developed in recent years.