## 4 Bioactive Properties  
### Antibacterial Effects  
Antibiotics, such as penicillin, tetracycline, ciprofloxacin, are a common class of antibacterial agents, which are specifically designed to target and kill or inhibit the growth of bacteria. Natural compounds can be used alongside antibiotics as complementary treatments, potentially enhancing the overall effectiveness of the treatment. The antibacterial effects of sesquiterpenes and sesquiterpene derivatives from _Ferula_ have been extensively studied. In 2001, [PERSON] et al. [64] isolated the daucane sesquiterpene ferutinin (**18**) from _F. kuhistanica_, which showed strong activity against Gram-positive bacteria, including _Staphylococcus aureus_, _S. epidermidis_, _Enterococcus faecalis_, and _Bacillus subtilis_, but did not exhibit activity against Gram-negative bacteria. Among them, the MIC values of ferutinin (**18**) were similar to those of the standard antibiotics ampicillin and  
Figure 8: Proposed biosynthetic pathways for sesquiterpene chromosomes [115; 143; 195]. chloramphenicol. In another study, [PERSON] et al. (2005) reported that fertuinin (**18**), feferin (**21**), and feferidin (**17**) from _F. hermonis_ showed strong activity against methicillin-resistant _S. aureus_ (MRSA) (MIC, <0.39, 1.56, and 0.78 \(\mathrm{\SIUnitSymbolMicro mL}\), respectively), _B. subtilis_ (MIC: <0.39, 1.56, and <0.39 \(\mathrm{\SIUnitSymbolMicro mL}\), respectively), _Mycobacterium tuberculosis_ (MIC: 2, 8, and 0.69 \(\mathrm{\SIUnitSymbolMicro mL}\), respectively), and BCG (MIC: 1.56, 6.25, and 3.125 \(\mathrm{\SIUnitSymbolMicro mL}\), respectively). In addition, the enhancing effect of fertuinin (**18**) on four antitubercular drugs, i.e., rifampin, isoniazid, streptomycin, and ethionamide was tested against _M. smegmatis_. Ferutinin (**18**) showed higher activity (MIC, 10 \(\mathrm{\SIUnitSymbolMicro mL}\)) than rifampin and streptomycin (MIC: each at 20 \(\mathrm{\SIUnitSymbolMicro mL}\)) in the agar dilution assay, and the combination of fertuinin (**18**) with the anti-tuberculosis drugs isoniazid and ethionamide resulted in enhancing the effect of the antimycobacterial activity in the checkerboard method, while the combination with rifampicin or streptomycin did not exhibit this effect (206). As another structural type of sesquiterpenes, the new guaianolides diversolide A (**103**), diversolide D (**106**), and diversolide F (**108**) from _F. diversitutta_ showed moderate antibacterial activities against _S. aureus_ (ATCC 29737) and _Escherichia coli_ (ATCC 8739), with MIC values ranging from 40 to 80 \(\mathrm{\SIUnitSymbolMicro mL}\), while the MIC values of the gentamycin positive control were 18 \(\mathrm{\SIUnitSymbolMicro mL}\) and 8 \(\mathrm{\SIUnitSymbolMicro mL}\), respectively (**49**). In 2004, the sesquiterpene coumarin ferulenol (**349**) and its three derivatives were investigated for their antimycobacterial activity against four strains of fast-growing _Mycobacterium_ species: _M. fortutium_, _M. phlei_, _M. aurum_, and _M. smegmatis_. Ferulenol (**349**) showed the most promising activity with IC\({}_{50}\) values of 0.5-2 \(\mathrm{\SIUnitSymbolMicro mL}\), which was superior to the therapeutically used antimycobacterials isoniazid and ethanbutot (IC\({}_{50}\): 0.5-8 \(\mathrm{\SIUnitSymbolMicro mL}\) and 0.5-4 \(\mathrm{\SIUnitSymbolMicro mL}\), respectively) (**207**). Ferulenol (**349**) showed stronger activity (MIC: each at 0.63 \(\mathrm{\SIUnitSymbolMicro mL}\)) against the above Gram-positive bacteria, and it exhibited potent activity against _Mycobacterium_ organisms (MIC: each at 1.25 \(\mathrm{\SIUnitSymbolMicro mL}\)). In contrast, ferchromone (**420**) proved to be less active (**208**). By the disk diffusion method, umbelliprenin (**150**) was found to have the highest activity against _B. subtilis_, _B. cereus_, _E. coli_, _Salmonella tythli_, _Klebsiella pounmoniae_, _S. aureus_, and _S. epidermidis_ at a concentration of 500 \(\mathrm{\SIUnitSymbolMicro mL}\)[209]. [PERSON] et al.