Synthesis, antimycobacterial, cytotoxicity, anti-inflammatory, in silico studies and molecular dynamics of pyrazole-embedded thiazolidin-4-one hybrids.

In the present investigation, we devolved and synthesized a new series of pyrazole-embedded thiazolidin-4-one derivatives (9a-p) with the goal to produce promising antitubercular leads. The in vitro antimycobacterial activity of the synthesized compounds was tested against replicating and nonreplicating Mtb H37Rv strains. With MIC ranging from 3.03 to 22.55 µg/ml, five compounds (9a, 9c, 9d, 9e, and 9f) emerged as promising antitubercular agents. The active molecules were nontoxic to normal Vero cells. All the synthesized compounds were evaluated for in vitro anti-inflammatory studies. Compounds 9a, 9b, 9c, 9h, and 9i exhibited excellent anti-inflammatory efficacy. Docking study was performed to understand the binding pattern of the significantly active compound 9a with 1P44.

(E)-3-(4-Chloro-phen-yl)-1-(2,3,4-trichloro-phen-yl)prop-2-en-1-one.

In the title chalcone derivative, C(15)H(8)Cl(4)O, the C=C double bond exists in an E configuration and the dihedral angle between the two benzene rings is 48.13 (11)°. In the crystal, mol-ecules are arranged into columns and stacked down the a axis featuring possible weak aromatic π-π stacking inter-actions [centroid-centroid separation = 3.888 (2) Å].

1-{1-[2,8-Bis(trifluoro-meth-yl)-4-quin-olyl]-5-methyl-1H-1,2,3-triazol-4-yl}ethanone.

There are two independent mol-ecules in the asymmetric unit of the title compound, C(16)H(10)F(6)N(4)O. The triazole ring is not coplanar with the quinoline ring system; the dihedral angle between the two planes being 74.47 (12) and 63.97 (13)° in the two mol-ecules. The crystal structure is characterized by inter-molecular C-H⋯F, C-H⋯N and C-H⋯O hydrogen bonding. Weak intra-molecular C-H⋯F inter-actions are observed. Disorder is observed in two F atoms of one of the trifluoro-methyl groups of one independent mol-ecule [occupancy ratios 0.77 (3):0.23 (3) and 0.77 (4):0.23 (4)] and in all three F atoms of one of the trifluoro-methyl groups of the second independent mol-ecule [occupancy ratios 0.520 (14):0.480 (14), 0.615 (17):0.385 (17) and 0.783 (11):0.217 (11)]. The O atom is also disordered over two positions with occupancies of 0.60 (13) and 0.40 (13) in the first mol-ecule.

4-Meth-oxy-benzaldehyde (5-bromo-pyrimidin-2-yl)hydrazone monohydrate.

In the title Schiff base compound, C(12)H(11)BrN(4)O·H(2)O, the organic mol-ecule exists in an E configuration with respect to the C=N double bond. The pyrimidine ring is approximately planar, with a maximum deviation of 0.011 (2) Å, and forms a dihedral angle of 10.68 (8)° with the benzene ring. In the crystal, inter-molecular O-H⋯N, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into a two-dimensional network parallel to the ac plane.

4-[4-Eth-oxy-carbonyl-5-(3,4-methyl-ene-dioxy-phen-yl)-3-oxocyclo-hex-1-en-1-yl]-3-phenyl-sydnone.

In the title compound {systematic name: 4-[4-eth-oxy-carbonyl-5-(3,4-methyl-ene-dioxy-phen-yl)-3-oxocyclo-hex-1-en-1-yl]-3-phenyl-1,2,3-oxadiazol-3-ium-5-olate}, C(24)H(20)N(2)O(7), the cyclo-hexene and dioxole rings adopt envelope conformations. The sydnone ring and the attached phenyl ring form a dihedral angle of 79.0 (1)°. In the mol-ecular structure, a C-H⋯O hydrogen bond generates an S(6) ring and a C-H⋯π inter-action involving the phenyl ring is observed. In the crystal structure, mol-ecules are linked into a ribbon-like structure along the a axis by C-H⋯O hydrogen bonds.

Pyridine- and Thiazole-Based Hydrazides with Promising Anti-inflammatory and Antimicrobial Activities along with Their In Silico Studies.

A new class of compounds formed by the linkage of -C(O)-NH- with pyridine and thiazole moieties was designed, synthesized, and characterized by various spectral approaches. The newly characterized compounds were evaluated for their antimicrobial as well as anti-inflammatory properties. The in vitro anti-inflammatory activity of these compounds was evaluated by denaturation of the bovine serum albumin method and showed inhibition in the range of IC50 values-46.29-100.60 µg/mL. Among all the tested compounds, compound 5l has the highest IC50 value and compound 5g has the least IC50 value. On the other hand, antimicrobial results revealed that compound 5j showed the lowest MIC values and compound 5a has the highest MIC values. Furthermore, molecular docking of the active compounds demonstrated a better docking score and interacted well with the target protein. Physicochemical parameters of the titled compounds were found suitable in the reference range only. The in silico molecular docking study revealed their COX-inhibitory action. Compound 5j emerged as a significant bioactive molecule among the synthesized analogues.