*Review* **Natural Bioactive Thiazole-Based Peptides from Marine Resources: Structural and Pharmacological Aspects**

**Rajiv Dahiya 1,\*,**†**, Sunita Dahiya 2,\*,**†**, Neeraj Kumar Fuloria 3, Suresh Kumar 4, Rita Mourya 5, Suresh V. Chennupati 6, Satish Jankie 1, Hemendra Gautam 7, Sunil Singh 8, Sanjay Kumar Karan 9, Sandeep Maharaj 1, Shivkanya Fuloria 3, Jyoti Shrivastava 10, Alka Agarwal 11, Shamjeet Singh 1, Awadh Kishor 12, Gunjan Jadon <sup>13</sup> and Ajay Sharma <sup>14</sup>**


Received: 25 May 2020; Accepted: 19 June 2020; Published: 24 June 2020

**Abstract:**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.

**Keywords:** azole-based peptide; marine sponge; peptide synthesis; cytotoxicity; cyanobacteria; thiazole; bioactivity

### **1. Introduction**

Heterocycles are known to govern a lot of processes of vital significance inside our body, including transmission of nerve impulses, hereditary information, and metabolism. A variety of the naturally occurring congeners, including reserpine, morphine, papaverine, and quinine, are heterocycles in origin, and many of the synthetic bioactives viz. methotrexate and isoniazid contain heterocyclic pharmacophores [1]. Among heterocycles, thiazoles have received special attention as promising scaffolds in the area of medicinal chemistry because this azole has been found alone or incorporated into the diversity of therapeutic active agents such as sulfathiazole, combendazole, niridazole, fanetinol, bleomycin, and ritonavir, which are associated with antibiotic, fungicidal, schistozomicidal, anti-inflammatory, anticancer, and anti-HIV properties [2,3]. Peptides are bioactive compounds of natural origin available in all living organisms and are known for their vital contribution in a wide array of biological activity. Due to their therapeutic abilities, peptides have received growing interest in recent years. In the human body, peptides perform a lot of essential functions including the engagement of peptide hormones like insulin, glucagon-like peptide-1 (GLP-1), and glucagon and in blood glucose regulation and are used to treat novel targets for certain disease conditions, including Alzheimer's disease, diabetes mellitus type 2, and obesity [4–7].

As unique structural features make azole-containing heterocyclic peptides (especially thiazoles) attractive lead compounds for drug development as well as nice tools for advance research, efforts should be made by scientists to develop biologically active thiazole-based peptide derivatives (TBPs). 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. Keeping in view the vital significance of TBPs, the current article focuses on different bioactive marine-derived thiazole-based polypeptides with complex structures and their potent resources, synthetic methodologies, stereochemical aspects, structural activity relationships, diverse modes of action, and bioproperties.
