Hydrobiological Aspects of Saturated, Methyl-Branched, and Cyclic Fatty Acids Derived from Aquatic Ecosystems: Origin, Distribution, and Biological Activity

This review focuses on the hydrobiological aspects of saturated, methyl-branched, and cyclic fatty acids (FA) derived from aquatic ecosystems. This short review presents the distribution of about 60 FA in various living organisms inhabiting the aquatic environment as well as in marine and freshwater sediments. In addition, it is important to determine the biological activity of saturated, methyl-branched, and cyclic fatty acids. An interesting finding was that some cyclic FA show antiplatelet activity. The generalized and presented data are of interest to hydrobiologists, chemists, and pharmacologists.


Acyclic Aliphatic Fatty (Carboxylic) Acids
The saturated FA shown in Figure 1 are the most abundant in a variety of natural sources. The first on this list is caprylic acid (1), which was first found in goat milk along with caproic acid (C6) and capric acid (2), and these acids together make up over 15% of the FA in goat milk fat [26,27].
It is known that monounsaturated and polyunsaturated FA possess many nutritional properties, and their main sources are marine red, brown, and green algae [48,[54][55][56][57][58][59]. Saturated FA have always been of less interest since they were assumed to have no practical value for human and animal health [60][61][62].

Comparison of Biological Activities of Natural Saturated Fatty Acids
It is known that the chemical structure of both natural molecules predetermines biological activity, which makes it possible to analyze the structure-activity relationships (SAR). This concept was first proposed by Brown and Fraser more than 150 years ago in 1868 [107]. According to other sources [108], SAR was used from the field of toxicology, according to which Cros, in 1863, determined the relationship between the toxicity of primary aliphatic alcohols and their solubility in water. More than 30 years later, Richet in 1893 [109], Meyer in 1899 [110], and Overton in 1901 [111] separately found a linear correlation between lipophilicity and biological effects. By 1935, Hammett [112,113] presented a method for accounting the effect of substituents on reaction mechanisms using an equation that considered two parameters: the substituent constant and the reaction constant. Complementing Hammett's model, Taft in 1956 proposed an approach to separate the polar, steric, and resonance effects of substituents in aliphatic compounds [114]. Combining all previous developments, Hansch and Fujita laid out the mechanistic basis for the development of the QSAR method [115], and the linear Hansch equation and Hammett's electronic constants are detailed in the book by Hansch and Leo published in 1995 [116].
Some popular computer programs can, with some degree of reliability, estimate the pharmacological activity of organic molecules isolated from natural sources or synthesized compounds [117][118][119]. It is known that classical SAR methods are based on the analysis of (quantitative) structure-activity relationships for one or more biological activities by using organic compounds belonging to the same chemical series as the training set [120].
The computer program PASS (prediction of activity spectra for substances), which has been continuously updated and improved for the past thirty years [121], is based on the heterogeneous training set algorithm, which includes information on more than 1.3 million known biologically active compounds that correlates with the data on about 10,000 types of biological activity [122]. Chemical descriptors implemented in PASS, which reflect the peculiarities of ligand-target interactions, and the original realization of the Bayesian approach for the elucidation of structure-activity relationships provide the average accuracy and predictivity for several thousand biological activities equal to about 96% [123]. In several comparative studies, it was shown that PASS outperforms, in predictivity, some other recently developed methods for the estimation of biological activity profiles [124,125]. Freely available via the Internet, the PASS Online web-service [126] is used by more than thirty thousand researchers from almost a hundred countries to determine the most promising biological activities for both natural and synthetic compounds [127,128]. To reveal the hidden pharmacological potential of the natural substances, researchers have successfully used the past fifteen years [129,130].
In the current study, we obtained PASS predictions for about 60 saturated fatty acids produced by different living organisms. PASS estimates are presented as Pa values, which correspond to the probability of belonging to a class of "actives" for each predicted biological activity. The higher the Pa value, the higher the confidence in the predicted biological activity [131].
Saturated FA (1-13) are complex lipids and are found in almost all living organisms. The biological activities of some of these acids have been studied and are shown in Table 1. The biological activity that was found using the PASS program is also provided in Table 1. For all saturated acids, the property as a regulator of lipid metabolism is dominant with a reliability of 86% to 91%. Of greatest interest are acids 9, 10, 11, and 12 since their reliability exceeds 91% and Figure 16 shows the 3D graph of the predicted and calculated biological activity of these saturated FA.  It is known that iso-FA (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), which are part of complex lipids and are found in almost all living organisms, are produced by many bacteria. The biological activity of some of these acids was studied and shown in Table 2, and the structures are shown in Figure 2. The biological activity that was found using the PASS program is provided in Table 2. For many iso-acids, the dominant property is as a regulator of lipid metabolism with a reliability of more than 81%. Among the published activities of iso-acids, anti-breast cancer activity is characteristic . Three acids 17, 18 and 19 are of interest since their reliability is 81% and Figure 17 provides the 3D graph of the predicted and calculated biological activity of these FA. Figure 16. The 3D graph shows the predicted and calculated biological activity of saturated FA (compound numbers: 9, 10, 11, and 12) showing the highest degree of confidence of more than 91%. The red zone is the dominant activity that is characteristic of all acids.  : 17, 18, and 19) showing the highest degree of confidence, more than 81%. In the red zone, there are two dominant activities (two peaks), which are characteristic of these acids. The first property is a regulator of lipid metabolism with a confidence level of 81%, and the second property is the treatment of precancerous conditions with a confidence level of more than 80%. Table 2. Biological activity of acyclic aliphatic iso-FA.

No.
Predicted Biological Activity, Pa * Reported Activity Ref. Anteiso-FA (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39), which are part of complex lipids, are found in almost all living organisms, and many bacteria produce them in significant quantities. The biological activity that was found using the PASS program is shown in Table 3, and the structures are shown in Figure 2. For many anteiso-acids, the dominant property is as a regulator of lipid metabolism with a confidence level of more than 91%. Of interest are four acids 30, 31, 35, and 39, and the reliability of their activity is more than 91%, and Figure 18 represents the 3D graph of the predicted and calculated biological activity of these anteiso-FA. Table 3. Biological activity of acyclic aliphatic anteiso-FA.

No.
Predicted Biological Activity, Pa *

Conclusions
This review focused on the hydrobiological aspects of saturated, methyl-branched, and cyclic FA derived from aquatic ecosystems and their distribution. The review presents about 60 that are found in various living organisms as well as in marine and freshwater sediments such as rivers, lakes, and sea bays. Particularly interesting was the determination of the biological activity of saturated, methyl-branched, and cyclic FA. The pharmacological activity of the presented acids was determined using the popular computer program PASS. According to PASS data, saturated FA are of interest as regulators of lipid metabolism as well as processes associated with the metabolism and synthesis of cholesterol. In addition, some acids exhibited antiviral and other properties. Methyl-branched acids exhibited similar properties. Interestingly, some cyclic FA exhibited antiplatelet, fibrinolytic, and anticoagulant activities. The obtained and presented data are of interest to hydrobiologists, biologists, chemists, and pharmacologists.
Funding: This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Institutional Review Board Statement: Not applicable.

Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.