Thiazole-Based Peptides | Encyclopedia MDPI

Thiazole-Based Peptides: Comparison

Please note this is a comparison between Version 2 by Rajiv Dahiya and Version 1 by Rajiv Dahiya.

Peptides are distinctive biomacromolecules that demonstrate potential cytotoxicity and diversified bioactivities against a variety of microorganisms including bacteria, mycobacteria, and fungi via their unique mechanisms of action. Among broad-ranging pharmacologically active peptides, natural marine-originated thiazole-based oligopeptides possess peculiar structural features along with a wide spectrum of exceptional and potent bioproperties. Because of their complex nature and size divergence, thiazole-based peptides (TBPs) bestow a pivotal chemical platform in drug discovery processes to generate competent scaffolds for regulating allosteric binding sites and peptide–peptide interactions. The present study dissertates on the natural reservoirs and exclusive structural components of marine-originated TBPs, with a special focus on their most pertinent pharmacological profiles, which may impart vital resources for the development of novel peptide-based therapeutic agents.

azole-based peptide
marine sponge
peptide synthesis
thiazole
cytotoxicity
cyanobacteria
bioactivity

1. Introduction

Thiazole-based peptides (TBPs) are obtained from diverse resources, primarily from cyanobacteria, sponges, and tunicates. A thiazole ring can be part of a cyclic structure or connected in a linear chain of peptides either alone or with other heterocycles like oxazole (e.g., thiopeptide antibiotics), imidazole, and indole (in the forms of histidine and tryptophan), thiazoline, oxazoline, etc. Cyclic peptides have an advantage over their linear counterparts as cyclization offers a reduction in conformational freedom, resulting in higher receptor-binding affinities. Understanding the structure–activity relationship (SAR), different modes of action, and routes of synthesis as tools are of vital significance for the study of complex molecules like heterocyclic bioactive peptides, which have a broad spectrum of pharmacological activities associated with them. Further, the sudden increase in the number of peptide drug products is another good reason to study this particular category of compounds on a priority basis.

2. Resources

Various natural sources of TBPs and other heterocyclic rings containing cyclopolypeptides comprise cyanobacteria [8–40], ascidians [41–62], marine sponges [63–70], and sea slugs [71–73]. Moreover, actinomycetes, sea hare, red alga, and higher plants [74–80] were found to be other potential resources of TBPs.

3. Biological Activity

Although thiazole-containing cyclopolypeptides of marine origin are associated with a number of bioactivities including antitubercular, antibacterial, antifungal, and inhibitory activity against serine protease enzymes chymotrypsin and elastase; anti-HIV activity; antiproliferative activity; antimalarial activity; and inhibitory activity against the transcription factor activator protein-1, the majority of them were found to exhibit anticancer activity. Various pharmacological activity-associated marine-derived Tzl-containing cyclopolypeptides along with susceptible cell line/organism with minimum inhibitory concentration are tabulated in Table 1.

Table 1. Heterocyclic Tzl-based peptides (TBPs) with diverse pharmacological activities.

TBPs	Resource	Bioactivity
TBPs	Resource	Susceptibilty	MIC^a Value
Haligramide A [63]	marine sponge Haliclona nigra	Cytotoxicity against A-549 (lung), HCT-15 (colon), SF-539 (CNS^b), and SNB-19 (CNS) human tumor cell lines	5.17–15.62 μg/mL
Haligramide B [63]	marine sponge Haliclona nigra	Cytotoxicity against A-549 (lung), HCT-15 (colon), SF-539 (CNS), and SNB-19 (CNS) human tumor cells	3.89–8.82 μg/mL
Scleritodermin A [64]	marine sponge Scleritoderma nodosum	Cytotoxicity against colon HCT116, ovarian A2780, and breast SKBR3 cell lines	0.67–1.9 μM
Obyanamide [12]	marine cyanobacterium Lyngbya confervoides	Cytotoxicity against KB^c and LoVo cells	0.58 and 3.14 µg/mL
Waiakeamide [66]	marine sponge Ircinia dendroides	Anti-TB activity against Mycobacterium tuberculosis	7.8 μg/mL
Ulongamide A [13]	marine cyanobacterium Lyngbya sp.	Cytotoxicity against KB and LoVo cells	1 and 5 µM
Guineamide B [14]	marine cyanobacterium Lyngbya majuscula	Cytotoxicity against mouse neuroblastoma cell line	15 µM
Calyxamide A [110]	marine sponge Discodermia calyx	Cytotoxicity against P388 murine leukemia cells	3.9 and 0.9 μM
Bistratamide J [50]	marine ascidian Lissoclinum bistratum	Cytotoxic activity against the human colon tumor (HCT-116) cell line	1.0 µg/mL
Didmolamide A and B [48]	marine tunicate Didemnum molle	Cytotoxicity against several cultured tumor cell lines (A549, HT29, and MEL28)	10–20 µg/mL
Aeruginazole A [91]	freshwater cyanobacterium Microcystis sp.	Antibacterial activity againt B. subtilis and S. albus Cytotoxicity against MOLT-4 human leukemia cell line and peripheral blood lymphocytes	2.2 and 8.7 μM 41 and 22.5 μM
Cyclotheonellazole A, B and C [68]	marine sponge Theonella aff. swinhoei	Inhibitory activity against serine protease enzyme chymotrypsin Inhibitory activity against serine protease enzyme elastase	0.62, 2.8, and 2.3 nM 0.034, 0.10, and 0.099 nM
Microcyclamide MZ602 [18]	cyanobacterium Microcystis sp.	Inhibition activity of chymotrypsin	75 μM
Dolastatin 3 [9]	marine cyanobacterium Lyngbya majuscula	Inhibition of HIV-1 integrase (for the terminal-cleavage and strand- transfer reactions)	5 mM and 4.1 mM
Lyngbyabellin A [27]	marine cyanobacterium Lyngbya majuscula	Cytotoxicity against KB cells (human nasopharyngeal carcinoma cell line) and LoVo cells (human colon adenocarcinoma cell line) Cytotoxicity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells Cytoskeletal-disrupting effects in A-10 cells	0.03 and 0.50 μg/mL 1.1 and 0.71 μM 0.01–5.0 μg/mL
Lyngbyabellin B [86]	marine cyanobacterium Lyngbya majuscula	Toxicity to brine shrimp (Artemia salina) Antifungal activity against Candida albicans (ATCC 14053) in a disk diffusion assay Cytotoxicity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells	3.0 ppm 100 μg/disk 1.1 and 0.71 μM
Lyngbyabellin E [28]	marine cyanobacterium Lyngbya majuscula	Cytotoxicity against NCI-H460 human lung tumor and neuro-2a mouse neuroblastoma cells Cytoskeletal-disrupting effects in A-10 cells	0.4 and 1.2 μM 0.01–6.0 μM
Lyngbyabellin H [28]	marine cyanobacterium Lyngbya majuscula	Cytotoxicity against NCI-H460 human lung tumor and neuro-2a mouse neuroblastoma cells	0.2 and 1.4 μM
Lyngbyabellin N [29]	marine cyanobacterium Moorea bouilloni	Cytotoxic activity against HCT116 colon cancer cell line	40.9 nM
27-Deoxy- lyngbyabellin A [30]	marine cyanobacterium Lyngbya bouillonii	Cytotoxicity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells	0.012 and 0.0073 μM
Lyngbyabellin J [30]	marine cyanobacterium Lyngbya bouillonii	Cytotoxicity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells	0.054 and 0.041 μM
Raocyclamide A [32]	filamentous cyanobacterium Oscillatoria raoi	Cytotoxicity against embryos of sea urchin Paracentrotus lividus	30 μg/mL (ED₁₀₀)^d
Tenuecyclamide A, C and D [105]	cultured cyanobacterium Nostoc spongiaeforme var. tenue	Cytotoxicity against embryos of sea urchin Paracentrotus lividus	10.8, 9.0, and 19.1 μM (ED₁₀₀)
Dolastatin I [75]	sea hare Dolabella auricularia	Cytotoxicity against HeLa S₃ cells	12 μg/mL
Marthiapeptide A [74]	marine actinomycete Marinactinospora thermotolerans SCSIO 00652	Antibacterial activities against Micrococcus luteus, Staphylococcus aureus, Bacillus subtilis, and Bacillus thuringiensis Cytotoxicity against SF-268 (human glioblastoma) cell line, MCF-7 (human breast adenocarcinoma) cell line, NCI-H460 (human lung carcinoma) cell line, and HepG2 (human hepatocarcinoma) cancer cell line	2.0, 8.0, 4.0, and 2.0 μg/mL 0.38, 0.43, 0.47, and 0.52 μM
Keramamide G, H and J [67]	marine sponge Theonella sp.	Cytotoxicity against L1210 murine leukemia cells and KB human epidermoid carcinoma cells	10 µg/mL
Keramamide K [109]	marine sponge Theonella sp.	Cytotoxicity against L1210 murine leukemia cells and KB human epidermoid carcinoma cells	0.72 and 0.42 µg/mL
Lissoclinamide 8 [55]	sea squirt Lissoclinum patella	Cytotoxicity against T24 (bladder carcinoma cells), MRC5CV1 (fibroblasts), and lymphocytes	6, 1, and 8 μg/mL
Mechercharmycin A [79]	marine bacterium Thermoactinomyces sp. YM3-251	Cytotoxic activity against A549 (human lung cancer) cells and Jurkat cells (human leukemia)	4.0 ´ 10⁻⁸ M and 4.6 ´ 10⁻⁸ M
Leucamide A [70]	marine sponge Leucetta microraphis	Cytotoxicity against HM02, HepG2, and Huh7 tumor cell lines	5.2, 5.9, and 5.1 μg/mL
Bistratamide H [50]	marine ascidian Lissoclinum bistratum	Cytotoxic activity against the human colon tumor (HCT-116) cell line	1.7 µg/mL
Patellamide E [58]	marine ascidian Lissoclinum patella	Cytotoxicity against human colon tumor cells in vitro	125 µg/mL
Microcyclamide [35]	cultured cyanobacterium Microcystis aeruginosa	Cytotoxicity against P388 murine leukemia cells	1.2 µg/mL
Dolastatin E [76]	sea hare Dolabella auricularia	Cytotoxicity against HeLa-S₃ cells	22–40 μg/mL
Aerucyclamide A [38]	freshwater cyanobacterium Microcystis aeruginosa PCC 7806	Antiparasite activity against Plasmodium falciparum K1 and Trypanosoma brucei rhodesiense STIB 900	5.0 and 56.3 μM
Aerucyclamide B [38]	freshwater cyanobacterium Microcystis aeruginosa PCC 7806	Antiparasite activity against Plasmodium falciparum K1 and Trypanosoma brucei rhodesiense STIB 900	0.7 and 15.9 μM
Aerucyclamide C [38]	freshwater cyanobacterium Microcystis aeruginosa PCC 7806	Antiparasite activity against Plasmodium falciparum K1 and Trypanosoma brucei rhodesiense STIB 900	2.3 and 9.2 μM
Aerucyclamide D [38]	freshwater cyanobacterium Microcystis aeruginosa PCC 7806	Antiparasite activity against Plasmodium falciparum K1 and Trypanosoma brucei rhodesiense STIB 900	6.3 and 50.1 μM
Aerucyclamide A, B and C [37,38]	freshwater cyanobacterium Microcystis aeruginosa PCC 7806	Grazer toxicity against the freshwater crustacean Thamnocephalus platyurus	30.5, 33.8, and 70.5 μM
Aerucyclamide B and C [38]	freshwater cyanobacterium Microcystis aeruginosa PCC 7806	Cytotoxic activity against Rat Myoblast L6 cells	120 and 106 μM
Urukthapelstatin A [78]	marine-derived bacterium Mechercharimyces asporophorigenens YM11-542	Cytotoxicity against A549 human lung cancer cells	12 nM
Mechercharmycin A [79]	marine-derived bacterium Thermoactinomyces sp.	Cytotoxicity against A549 human lung cancer cells and Jurkat cells	4.0 ´ 10^-8 M and 4.6 ´ 10^-8 M
Ulithiacyclamide [56,117]	marine tunicate Lissoclinum patella	Cytotoxic activity against L1210, MRC5CV1, T24, and CEM cell lines (continuous exposure)	0.35, 0.04, 0.10, and 0.01 μg/mL
Ulicyclamide [117]	marine tunicate Lissoclinum patella	Cytotoxic activity against L1210 murine leukemia cells	7.2 μg/mL
Patellamide A [117]	marine tunicate Lissoclinum patella	Cytotoxic activity against L1210 murine leukemia and human ALL cell line (CEM)	3.9 and 0.028 μg/mL
Patellamide B, C [117]	marine tunicate Lissoclinum patella	Cytotoxic activity against L1210 murine leukemia cells	2.0 and 3.2 μg/mL
Venturamide A [34]	marine cyanobacterium Oscillatoria sp.	Antiparasitic activity against Plasmodium falciparum, Trypanasoma cruzi Cytotoxicity against mammalian Vero cells and MCF-7 cancer cells	8.2 and 14.6 μM 86 and 13.1 μM
Venturamide B [34]	marine cyanobacterium Oscillatoria sp.	Antiparasitic activity against Plasmodium falciparum, Trypanasoma cruzi Cytotoxicity against mammalian Vero cells	5.2 and 15.8 μM 56 μM
Bistratamides A and B [60]	aplousobranch ascidian Lissoclinum bistratum	Cytotoxicity against MRC5CV1 fibroblasts and T24 bladder carcinoma cells	50 and 100 µg/mL
Bistratamide M [61]	marine ascidian Lissoclinum bistratum	Cytotoxicity against breast, colon, lung, and pancreas cell lines	18, 16, 9.1, and 9.8 μM
Balgacyclamide A [33]	freshwater cyanobacterium Microcystis aeruguinosa EAWAG 251	Antimalarial activity against Plasmodium falciparum K1	9 and 59 μM
Balgacyclamide B [33]	freshwater cyanobacterium Microcystis aeruguinosa EAWAG 251	Antiparasitic activity against Trypanosoma brucei rhodesiense STIB 900	8.2 and 51 μM

^aMIC—minimum inhibitory concentration, ^b CNS—central nervous system, ^c KB—ubiquitous KERATIN-forming tumor cell subline, ^dED₁₀₀—effective dose for 100% inhibition.