Thiophene Ring-opening Reactions III: One-Pot Synthesis and Antitumor Activity of 1,3,4-Thiadiazoline-Benzothiazolo[3,2-b]pyridazine Hybrids†.

INTRODUCTION: The preparation of model 6-chloro-5-nitrothieno[2,3-c]pyridazines incorporating (2'-halo-5'-nitrophenyl) entity is described. Interaction of these substrates with N'-(aryl)benzothiohydrazides, in the presence of triethylamine, followed a formal [4+1] annulation, furnishing the respective 1,3,4-thiadiazoline-benzothiazolo [3,2-b]pyridazine hybrids directly. This one-pot synthesis implies thiophene ring-opening and two consecutive intramolecular cyclizations. The structures of the synthesized new hybrids are supported by MS, NMR, and IR spectral data and further confirmed by single-crystal X-ray diffraction. These hybrids exhibit antiproliferative activity with notable selectivity against solid tumor cell lines (IC50: 4-18 µM). AIMS: This study aimed at exploring the scope and applicability of thiophene ring-opening reaction towards the synthesis of new thiadiazoline-[fused]tricyclic conjugates. BACKGROUND: α-Chloro-ß-nitrothienopyridazine underwent ring-opening upon reacting with N'-(aryl)benzothiohydrazides generating 1,3,4-thiadiazoline-benzothiazolo[3,2-b]pyridazines. OBJECTIVE: This new thiophene ring-opening reaction is applied to the one-pot synthesis of thiadiazoline-benzothiazolo[3,2-b]pyridazine couples. METHOD: A direct interaction of α-chloro-ß-nitrothienopyridazine with N'-(aryl)benzothio-hydrazide at room temperature for 1-2 h occurred. RESULT: a-Chloro-ß-nitrothieno[2,3-c]pyridazines are suitable substrates for the facile synthesis of thiadiazoline-benzothiazolo[3,2-b]pyridazine hybrids. CONCLUSION: This novel ring-opening reaction proceeds via formal [4+1] annulation and provides a versatile approach to various conjugated and/or fused five-membered heterocycles.

Ultrasound-assisted synthesis of two novel [CuBr(diamine)2·H2O]Br complexes: Solvatochromism, crystal structure, physicochemical, Hirshfeld surface thermal, DNA/binding, antitumor and antibacterial activities.

Two new hydrated monocationic Cu(II) complexes with 1,3-propylenediamine and 1,2-ethylenediamine of general formula [CuBr(N-N)2·H2O]Br were prepared. The complexes were identified by means of several spectroscopic tools (Uv-visible, IR and MS), thermally (TG/DTA) and CHN-elemental analysis. The three dimensional structure for complex A and B was provide by X-ray diffraction studies and showed the Cu(II) ion as 4 + 1 + 1 coordinated, four nitrogen atoms of the diamine ligands, one bromide ion and one H2O semi-coordinated to the Cu(II) center, a typical trans effect is clearly observed in the two complexes. The molecular crystal structures are linked via several H-bonds like N_H…Br and N_H…O. Additionally, intra-molecular H-bonds of kind C_H…Br is observed; these interactions lead to crystal structure three dimensional architecture packing. Hirshfeld surfaces (HSA) analysis was served to figure out the inter-contacts and fingerprints atoms percentage. DNA-binding, antitumor and antibacterial effectiveness of the desired complexes were evaluated.