Herbal Metabolites as Potential Carbonic Anhydrase Inhibitors: Promising Compounds for Cancer and Metabolic Disorders.

Background: Human carbonic anhydrases (CAs) play a role in various pathological mechanisms by controlling intracellular and extracellular pH balance. Irregular expression and function of CAs have been associated with multiple human diseases, such as obesity, cancer, glaucoma, and epilepsy. In this work, we identify herbal compounds that are potential inhibitors of CA VI. Methods: We used the AutoDock tool to evaluate binding affinity between the CA VI active site and 79 metabolites derived from flavonoids, anthraquinones, or cinnamic acids. Compounds ranked at the top were chosen for molecular dynamics (MD) simulations. Interactions between the best CA VI inhibitors and residues within the CA VI active site were examined before and after MD analysis. Additionally, the effects of the most potent CA VI inhibitor on cell viability were ascertained in vitro through the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Results: Kaempferol 3-rutinoside-4-glucoside, orientin, kaempferol 3-rutinoside-7-sophoroside, cynarin, and chlorogenic acid were estimated to establish binding with the CA VI catalytic domain at the picomolar scale. The range of root mean square deviations for CA VI complexes with kaempferol 3-rutinoside-4-glucoside, aloe-emodin 8-glucoside, and cynarin was 1.37 to 2.05, 1.25 to 1.85, and 1.07 to 1.54 Å, respectively. The MTT assay results demonstrated that cynarin had a substantial effect on HCT-116 cell viability. Conclusion: This study identified several herbal compounds that could be potential drug candidates for inhibiting CA VI.

Tuning Polymorphs and Morphology of Microbially Induced Calcium Carbonate: Controlling Factors and Underlying Mechanisms.

Microbially precipitated calcium carbonate (CaCO3) has drawn broad attention due to its potential applications in various areas, for example, biocementation, medicine, and soil reinforcement. Sporosarcina pasteurii (S. pasteurii), formerly known as Bacillus pasteurii, has been investigated for CaCO3 biomineralization due to its high ureolytic activity. A high degree of supersaturation with respect to the presence of bacterial cell wall, extracellular polymeric substances, and organic byproducts of bacterial activity plays an important role in the formation and stabilization of CaCO3 polymorphs. Although microbially induced CaCO3 and its polymorphs have been investigated broadly, the mechanisms of polymorph selection and morphological evolution are not well understood. This study employs ex situ approaches to address the complication of biomineralization in the presence of living organisms and to elucidate how solution chemistry, bacterial activity, and precipitation kinetics alter the polymorphism and morphology of CaCO3 induced by S. pasteurii. The results indicate that in the presence of enough calcium ions and urea (as a carbonate source), the bacterial activity favors the formation and stabilization of vaterite. The morphological observations also provide valuable information on the particles' microstructure. The morphology of calcite evolves from single crystal to polycrystalline structures, and the morphology of vaterite evolved from spherical to oval-shaped structures on increasing the organic material concentration. Specific functional groups also exert morphological control on CaCO3 polymorphs. However, the sensitivity of the calcite polymorph to the composition and orientation of these functional groups is higher compared to that of the vaterite polymorph. These findings offer important insights that can be used to constrain a set of experimental conditions for synthesizing a certain polymorph ratio for vaterite/calcite or a particular morphology of each polymorph and shed light on the crystallization and phase transformation mechanisms in such complicated bioenvironments.