The β-lactams constitute a well-known class of compounds having tremendous biological significance. Besides being a motif of biological interest, they serve as versatile synthons in organic chemistry. In fact, their easy accessibility in the laboratory by several methods combined with inherent reactivity of the β -lactam ring due to ring-strain places it among the most sought for substrate in the arsenal of synthetic organic chemists. Several chemical reagents, heat, and light promote its ring-opening, ring-expansions and rearrangement reactions yielding a wide variety of biologically relevant nitrogen-containing acyclic and heterocyclic compounds. In recent years, the reactivity of differently functionalized β-lactam rings towards diverse kinds of reagents has been investigated. These investigations exploit selective bond cleavage of the β-lactam nucleus via N1-C2, C3- C4, C2-C3 or N1-C4 bond cleavage using simple reagents. The reduction of amide carbonyl group, thionation, and pyrolysis/photolysis have also been explored. These investigations have led to the discovery of many easy synthetic methods for biologically important classes of compounds such as β-amino acids, β-amino esters, amino sugars, amino alcohols, peptides, azetidines, and other heterocyclic compounds. This article discusses the advances made in the studies on the reactivity of β- lactam ring during the last ten years.

Thiazole-pyrazoline Schiff base hybrids have a broad range of pharmacological potential with an ability to control the activity of numerous metabolic enzymes. In this work, a greener and more efficient approach has been developed to synthesize a novel series of thiazole-pyrazoline Schiff base hybrids using ZnO nanoparticle-assisted protocol in good to excellent yields (78.396.9) and examined their antibacterial activity against Gram-positive and Gram-negative bacteria, as well as their antioxidant activity. Compound 24 (IZD=18.67±0.58) displayed better activity against P. aeruginosa compared with amoxicillin (IZD=14.33±2.52) at 250μg/mL, whereas compounds 22 and 24 (IZD=13.33±0.58mm and 17.00±1.00mm, respectively) showed better activity against E. coli compared with amoxicillin (IZD=14.67±0.58mm) at 500μg/mL. The remaining compounds showed moderate to weak activity against the tested bacterial strains. Compound 21 displayed significant inhibition of DPPH (IC₅₀=4.63μg/mL) compared with ascorbic acid (IC₅₀=3.21μg/mL). Compound 21 displayed 80.01±0.07 inhibition of peroxide formation, suggesting its potential in preventing the formation of lipid peroxides. The results of the ADMET study showed that all synthesized compounds obeyed Lipinski's rule of five. In silico pharmacokinetic study demonstrated that compound 24 had superior intestinal absorption compared with amoxicillin. In silico molecular docking analysis revealed a binding affinity of 9.9Kcal/mol for compound 24 against PqsA compared with amoxicillin (7.3Kcal/mol), whereas compounds 22 and 24 displayed higher binding affinity (8.5 and 7.9Kcal/mol, respectively) with DNA gyrase B compared with amoxicillin (-7.1Kcal/mol), in good agreement with in vitro antibacterial activity against P. aeruginosa and E. coli. In silico toxicity study showed that all synthesized compounds had LD₅₀ (mg/kg) values ranging from 800 to 1,000 putting them in ProTox-II class 4. The in vitro antibacterial activity and molecular docking analysis showed that compound 24 is a promising antibacterial therapeutic agent against P. aeruginosa and E. coli and compound 22 is a promising antibacterial agent against E. coli, whereas compound 21 is found to be a potential natural antioxidant agent. Moreover, the green synthesis approach using ZnO nanoparticle as catalyst was found to be a very efficient method to synthesize biologically active thiazole-pyrazoline Schiff base hybrids compared with the conventional method.

Prostate cancer is a leading killer disease among men all over the world. Inducing apoptosis (programmed cell death) is a strategic chemotherapeutic approach. Caspase-3 is a key effector of apoptosis, and its activation promotes apoptosis. It was hypothesized that erythrinaline alkaloids activate caspase-3. The alkaloids were isolated from the flowers and pods of Erythrina lysistemon. Their effect on human recombinant caspase-3 was studied. This study reports that three erythrinaline alkaloids (+)-11α-hydroxyerysotrine N-oxide (1), (+)-11β-hydroxyerysotrine N-oxide (2) and (+)-11β-methoxyerysotrine N-oxide (3) activated human recombinant caspase-3 in a dose-dependent manner. Compound 1 and 2 increased the activity by five-fold while compound 3 increased it by ten-fold. Erythrinaline alkaloids exhibit remarkable ability to activate caspase-3 and may be lead compounds as potential therapeutics for the treatment of cancer as inducers of apoptosis in cancer cells. Key words: Erythrinaline alkaloids, human recombinant caspase-3, apoptosis, prostate cancer.