Lupeol, a novel anti-inflammatory and anti-cancer dietary triterpene

Beneficial health effects of lupeol triterpene: A review of preclinical studies

Recent advances of pyrazole-containing derivatives as anti-tubercular agents.

Pentacyclic lupane-type triterpenes, exemplified by lupeol [lup-20(29)-en-3b-ol], principally found in common fruit plants such as olive, mango, strawberry, grapes, etc., were reported to possess beneficial effects as a therapeutic and preventive agent for a range of disorders. Although lupeol exhibits an array of biological activities like anti-inflammatory and anti-arthritic activities both in in vitro and in vivo systems, extensive exploration to establish its role as a chemopreventive compound is warranted. Last 15 years have seen tremendous efforts by researchers worldwide to develop this wonderful molecule for its clinical use toward the treatment of a variety of disorders. These studies also provide insight into the mechanism of action of lupeol and suggest that it is a multi-target agent with immense anti-inflammatory potential targeting key molecular pathways which involve nuclear factor kappa B (NF-jB), cFLIP, Fas, Kras, phosphatidylinositol-3-kinase in a variety of cells. It is noteworthy that lupeol at its effective therapeutic doses exhibits no toxicity to normal cells and tissues. The perception of chemoprevention lies still in its infancy. Intervention to slow down, arrest or reverse the process of carcinogenesis by the use of either natural or synthetic substances individually or in combination therapy has emerged as a promising and pragmatic medical approach to reduce cancer risk.

Biological Activities of Lupeol

Therapeutic evolution of benzimidazole derivatives in the last quinquennial period.

Wound healing activity and docking of glycogen-synthase-kinase-3-β-protein with isolated triterpenoid lupeol in rats

Synthesis and biological evaluation of new imidazo[2,1-b][1,3,4]thiadiazole-benzimidazole derivatives

A new series of pyrazole-based 1,2,3-triazole derivatives (6a–x) were synthesized by employing click reaction using a 2:1 mixture of PEG-400 and water as green solvent. The synthesized intermediate and final compounds were characterized by 1H NMR, 13C NMR, and mass spectra and elemental analysis techniques. The structure of one of the final compounds, 6a was evidenced by single crystal X-ray diffraction study. Among the twenty-four compounds, five compounds (6a, 6b, 6d, 6f, and 6g) showed significant antitubercular activity against Mycobacterium tuberculosis H37Rv with a minimum inhibitory concentration (MIC) ≤ 6.25 µg/mL. The 4-(((5-(4-Chlorophenyl)-1-phenyl-1H-pyrazol-3-yl)methoxy)methyl)-1-cyclohexyl-1H-1,2,3-triazole (6g) was the most potent compound of the series, which showed a MIC of 3.13 µg/mL. The cytotoxicity study of active anti-TB compounds on normal Vero cells revealed that the compounds are non-toxic with a high selectivity index (>37). Most of the pyrazole-1,2,3-triazole derivatives with a 4-chlorophenyl substitution at position-5 of the pyrazole ring showed a better anti-TB activity than the corresponding 4-bromophenyl or 4-methoxyphenyl substituted derivatives. The target compounds were also evaluated for their in vitro antibacterial activity and six compounds (6a, 6c, 6d, 6e, 6l, and 6w) showed promising inhibition activity against four tested strains.
 A new series of pyrazole-1,2,3-triazole derivatives were synthesized by employing a multicomponent one pot click reaction. The most potent anti-TB agent of the series showed a MIC of 3.13 µg/mL.

Synthesis of new pyrazole-triazole hybrids by click reaction using a green solvent and evaluation of their antitubercular and antibacterial activity

Acacia auriculiformis is an agro-forestry species in India with application in paper industry. The species is saline intolerant and fails to establish. Experiments were conducted to induce saline tolerance in callus cultures of A. auriculiformis on Murashige & Skoogs medium supplemented with different concentrations of NaCl+CaCl2––– (2:1; 50, 100, 150, 200, 250 or 300 mM). Calli were trained for eight sub-culture generations. The genome from saline-tolerant calli was extracted by modified cetyl trimethyl ammonium bromide method and subjected to polymerase chain reaction-based random amplified polymorphic DNA technique. The polymorphic DNA bands were eluted and cloned to Escherichia coli with the help of pTZ57R/T. The transformed plasmid DNA was sequenced and subjected to BLAST at National Center for Biotechnology Information. Results indicated that saline training of calli resulted in the expression of tolerance to 100 and 150 mM saline concentration after eight sub-cultures. Both the saline concentration...

PCR-based RAPD technique to determine induced salinity tolerance in vitro in Acacia auriculiformis

For any antimicrobial assay, a standard drug is used to compare the bactericidal efficiency of the bioactive compound under screening. The standard drugs have different targets that may be intracellular or membrane located. The location of the target is believed to be determining the bioactivity of the drug depending on the drug's access to its target. Therefore, different drugs must have a different magnitude in exhibiting the biological effect. However, in most of the published literature about the screening of bioactive compounds on antimicrobial activity, generally, the standard drug is randomly chosen while comparing against the bioactive compound of interest. Further, the antimicrobial activity is inferred by comparing the randomly chosen standard drugs without knowing the physicochemical parameters of the standard drug and the test molecule. It is just like an unfair comparison of the impact of a bullet with the impact of an explosive in a combat scene. Computer-based strategies for structure-based drug discovery presents a valuable alternative to the costly and time-consuming process of random screening. The docking studies provide better insights into the binding mechanism of substrate and inhibitor at the molecular level. The evaluation of such a comparison of bioactive compounds against randomly selected standard drugs through a customized virtual screening pipeline showed 57% false positives, 18% true positive, 17% true negative, 8% false-negative results. This study directs for mandatory cheminformatics-based assessment of the bioactive compounds before choosing the standard drug to compare with.

H. S. Santosh Kumar

Papers

Wound healing activity and docking of glycogen-synthase-kinase-3-β-protein with isolated triterpenoid lupeol in rats

Synthesis and biological evaluation of new imidazo[2,1-b][1,3,4]thiadiazole-benzimidazole derivatives

Synthesis of new pyrazole-triazole hybrids by click reaction using a green solvent and evaluation of their antitubercular and antibacterial activity

PCR-based RAPD technique to determine induced salinity tolerance in vitro in Acacia auriculiformis

Molecular docking studies of gyrase inhibitors: weighing earlier screening bedrock