Recent Advances in the Synthesis and Biological Activities of Quinolactacin and Its Derivatives: A Comprehensive Review

As we know that, Oxadiazole is a heterocyclic compound containing an oxygen atom and two nitrogen atoms in a five-membered ring and is derived from furan by substitution of two methylene groups (=CH) with two pyridine type nitrogen (-N=) [1,2]. There are three known isomers that is 1,2,4-oxadiazole, 1,2,3-oxadiazole and 1,2,5-oxadiazole (Figure 1.0). However, 1,3,4-oxadiazole and 1,2,4-oxadiazole are better known, and more widely studied by researchers because of their many important chemical and biological properties. Among heterocyclic compounds, 1,3,4-oxadiazole has become an important construction motif for the development of new drugs. Compounds containing 1,3,4-oxadiazole cores have a broad biological activity spectrum including antibacterial, antifungal, analgesic, anti-inflammatory, antiviral, anticancer, antihypertensive, anticonvulsant, and anti-diabetic properties. They have also attracted interest in medicinal chemistry as surrogates (bioisosteres) for carboxylic acids, esters and carboxamides. The ability of 1,3,4-oxadiazole heterocyclic compounds to undergo various chemical reactions has made them important for molecule planning because of their privileged structure, which has enormous biological potential. Some examples of compounds containing the 1,3,4-oxadiazole unit currently used in clinical medicine are: Raltegravir as an antiretroviral drug and Zibotentan as an anticancer agent. They possesses various other biological activities and having various synthetic approaches, some of them are presented here in the aritcle. Keywords: Oxadiazoles synthetic approaches, biologically active ozadiazoles, oxadiazoles as anticancers etc.

Xanthene derivatives are a notable class of heterocyclic compounds widely studied for their significant biological impact. These molecules, found in both natural and synthetic forms, have attracted substantial scientific interest due to their broad spectrum of biological activities. The xanthene nucleus, in particular, is associated with a range of potential pharmaceutical properties, including antibacterial, antiviral, antiinflammatory, anticancer, and antioxidant effects. Their structural flexibility allows for modifications that can enhance specific biological functions, making them valuable candidates in medicinal chemistry and drug development. Multi-component reactions involving two equivalents of 5,5-dimethylcyclohexane-1,3-dione with aromatic aldehydes yield xanthene derivatives that are known for their biological activity. Additionally, fused xanthene derivatives are formed through subsequent heterocyclization reactions, resulting in compounds with a broad range of biological properties. Various Xanthene derivatives incorporating thiophene and thiazole moieties were synthesized. Compounds 3a-c were further subjected to heterocyclization reactions to produce fused xanthene derivatives with additional heterocyclic components, enhancing their biological activity. The cytotoxic effects of the synthesized compounds were assessed across six cancer cell lines. Inhibition studies on c-Met kinase and the PC-3 cell line were conducted. Additionally, the compounds' inhibitory activity against tyrosine kinases was evaluated, and morphological changes in the A549 cell line were observed with the two most potent compounds. The synthesized heterocyclic compounds, derived from 5,5-dimethylcyclohexane-1,3-dione and related cyclohexanone derivatives, exhibited significant inhibitory effects across various cancer cell lines. Specifically, compounds 3b, 5c, 5d, 7b, 7c, 7d, 9a, 9b, 10b, 10c, 12c, 15b, 15c, 16b, 16c, 17c, 17d, 17e, and 17f demonstrated high levels of inhibition, indicating potential for further exploration of xanthene-based heterocyclic compounds to enhance anticancer properties.

Imidazothiazole and related heterocyclic systems. Synthesis, chemical and biological properties.

Mannich bases, synthesized through the reaction of an aldehyde, a primary or secondary amine, and a compound bearing an acidic hydrogen atom, represent a versatile class of scaffolds in medicinal chemistry. This review explores their broad spectrum of biological activities, emphasizing their potential in combating infectious diseases. With demonstrated efficacy against bacteria, fungi, and parasites, Mannich bases stand out as promising candidates for the development of novel therapeutic agents. Their versatility arises from the ability of their electronic, steric, and conformational parameters to modulate receptor interactions, significantly expanding their applicability in drug design. The review provides an in-depth analysis of the structure-activity relationship (SAR) of Mannich bases, highlighting how specific structural modifications enhance their biological activity. Additionally, it examines the lipophilic properties of these compounds, offering key insights into their influence on pharmacokinetics and pharmacodynamics. This understanding is essential for optimizing the development of novel therapeutics, particularly for addressing challenging infectious diseases. By integrating these aspects, this review underscores the pivotal role of Mannich bases in overcoming current challenges in drug resistance and shaping the future of drug discovery and development.

Chapter 25 - New challenges in drug discovery

Despite the large progress in medicine and pharmacy in the last few decades, traditional treatment of bacterial or viral diseases is frequently ineffective and is connected with some side effects. Currently, there is observed an increasing interest in natural plant-derived substances as a potential and promising group of medicines in prevention and treatment of several infectious diseases. Terpenes and their derivatives are a large class of natural organic components of essential oils and are widespread in the plant kingdom. Numerous experimental studies have shown that essential oils exhibit a large spectrum of biological and pharmacological activities in vitro. Herbal essential oils have been proved to possess antimicrobial, antiviral, antifungal and antiparasitic properties. They have also been reported to exhibit anti-inflammatory and immunostimulatory activities. Based on the wide spectrum of various biological activities, essential oils and terpenes commonly found in fruit, vegetables, herbs etc. have been suggested to constitute a novel group of preventive and therapeutic agents. Further experiments are necessary to confirm their pharmacological effectiveness, to determine potential toxic effects and the mechanism of their activity in in vivo models. This article describes the biological and pharmacological properties of herbal essential oils and some of their components, and summarizes the future prospects of potential application of essential oils in the prevention and treatment of infectious human diseases. In this review also possible mechanisms of their biological action are presented.

ing five and six member rings having hetero atoms such as N, O, S, P, Si and B etc. Many heterocyclic compounds are employed in the treatment of infectious diseases due to their specific antimicrobial activity. Heterocyclic compounds have attracted the attention of medicinal chemists because of having broad spectrum of pharmacological activities and hence it continues to yield new therapeutic agents. One such medicinal important heterocyclic nucleus is oxadiazole moiety. Oxazole is the parent compound for a vast class of heterocyclic aromatic organic compounds. These are azoles with an oxygen and a nitrogen separated by one carbon Oxazoles are aromatic compounds but less so than the thiazoles. Oxazole is a weak base

Research and development for neglected diseases: more is still needed, and faster.

To increase the success rate of drug discovery, one practical strategy is to begin molecular hybridisation. The presence of two or more pharmacophores in a single unit leads to a pharmacological potency greater than the sum of each individual moiety's potency. Heterocyclic compounds are very widely distributed in nature and are essential for life activities. Benzimidazole and oxadiazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties. The drug-like properties (like pharmacokinetics and pharmacodynamics) of the individual scaffolds can be improved by benzimidazole-oxadiazole chimeric molecules via a molecular hybridisation approach. Benzimidazole and oxadiazole cores can either be fused or incorporated using either functional groups/bonds. Over the last few decades, drug discovery scientists have predicted that these moieties could be interconnected to yield a novel or modified hybrid compound. Benzimidazole and oxadiazole hybrids were identified as the most potent anticancer, antimicrobial, anti-inflammatory, antioxidant, anticonvulsant, antidepressant, antihypertensive and antitubercular agents. In this context, the present review describes the biological properties of benzimidazole-oxadiazole (1,3,4 and 1,2,4) hybrids, their possible structure-activity relationship and the mechanism of action studies presented. This review article is intended to stimulate fresh ideas in the search for rational designs of more active and less toxic benzimidazole-oxadiazole hybrid prospective therapeutic candidates, as well as more effective diagnostic agents and pathologic probes.

Heterocyclic compounds have diverse biological activities and potential in drug development. This study aims to synthesize novel compounds with two 1,2,4-triazole cores and evaluate their biological properties, particularly their inhibitory activity against thymidine phosphorylase (TP), an enzyme involved in various physiological processes. The compounds were synthesized by reacting 5,5'-butane-bis-1,2,4-triazole derivatives with prenyl bromide. Characterization involved various techniques, including spectroscopy and elemental analysis. Antimicrobial potential was evaluated against bacteria and fungi, with comparative antibiotics as references. Inhibitory activity against TP was assessed, and molecular docking studies were conducted. Six compounds were successfully synthesized and their structures confirmed. The synthesized triazole derivatives exhibited high biological activity, with compounds 2 and 6 showing the most promising TP inhibition. Molecular docking studies revealed interactions between compound 2 and TP, involving nine amino acids. The synthesis of novel compounds with two 1,2,4-triazole cores contributes significantly to bis-triazole research. These compounds have potential as anti-tumor agents due to their inhibitory activity against TP, a crucial enzyme in tumor growth and metastasis. Comparative evaluation against antibiotics highlights their potency. Docking results provide insights into their interactions with TP, supporting their potential as potent TP inhibitors. Further research should focus on evaluating their efficacy in biological models, understanding their mechanisms of action, and optimizing their activities. The synthesized compounds with two 1,2,4-triazole cores exhibit significant biological activity, including strong TP inhibition and broad-spectrum antimicrobial effects. These findings emphasize their potential as anti-tumor agents and the need for further exploration and optimization. Future research should focus on evaluating their efficacy in biological models, understanding their mechanisms of action, and developing more potent bis-triazole derivatives for drug discovery efforts. The combined results from assays and docking studies support the therapeutic potential of these compounds as anti-tumor agents.

Heterocyclic compounds are fundamental in natural products and pharmaceuticals. The triazole nucleus, in particular, is a versatile structure present in numerous bioactive molecules. 7- chloroquinoline is historically significant for its antimalarial properties and exhibits a broad spectrum of biological activities, including antiviral, anticancer, antibacterial, and anti-inflammatory effects. This review aimed to compile and discuss 69 biologically active 1,2,3-triazole hybrids derived from 7-chloroquinoline, highlighting their enhanced bioactivity when combined with 4,7- dichloroquinoline. A comprehensive review of the literature was conducted to identify and analyze the synthesis and biological activities of triazole hybrids originating from 4,7- dichloroquinoline and 7-chloroquinoline. It was found that the 4,7-dichloroquinoline scaffold, when coupled with triazole derivatives, exhibited enhanced bioactivity, including antimicrobial, antimalarial, and anticancer effects. This synergy between the two structures underscores their potential therapeutic applications. The insights provided in this review will serve as a valuable resource for medicinal chemists exploring triazoles derived from 4,7-dichloroquinoline and 7- chloroquinoline. The enhanced bioactivity of these hybrids highlights their significance in the development of new therapeutic agents.

where the biological activity is expressed as the reciprocal of the concentration that elicit a given biological, pharmacological or toxicological endpoint such as ED 50 (effective dose 50%), IC 50 (inhibitory concentration 50%) or LD 50 (lethal dose 50%), and where x i is the i predictor (from a set of n predictors) raised to the powers from 1 to m and weighted by its coefficients a ij obtained from a multivariate statistical fitting [4,5]. Usually, most of the coefficients a ij can be zero, leading to much simpler looking QSAR models than the general form in Equation 1, as in the example below. Often, other functions of x i are used in the QSAR model such as the logarithmic or exponential function instead of a simple power expansion as in Equation 1. As a simple illustration of the operation of Equation 1 is the following example of a QSAR model to predict the inhibitory effect of 3-nitroflavones (3NF) based on a single predictor, x (the energy of the highest occupied molecular orbital, E HOMO ) raised to the power 1 (see also [6]). Invasive tumor growth and metastasis are sustained by angiogenesis (the formation of new blood vessels [7,8]), which led Folkman to suggest anticancer therapies by the use of antiangiogenic agents [9,10]. Lichtenberg et al. have shown that the antiangiogenicity of six 3NF is correlated with the energies of the highest occupied molecular orbital, E HOMO, the lower the oxidation potential the greater the inhibitory effects on several biomarkers of angiogenesis [11,12]. These authors report the following correlation between the E HOMO and the IC 50 of six 3NF for inhibition of proliferation of microvascular endothelial HMEC-1 cells after 72 h of incubation:

Introduction. In modern conditions, where military conflicts are accompanied by significant psychological and physical stress on participants, the development of effective antiepileptic drugs has become one of the key challenges in medicine. This issue is particularly relevant due to the increasing number of cases of traumatic brain injuries, concussions, and other stress-related damages that can provoke convulsive states. In this context, derivatives of 1,2,4-triazole, which possess a broad spectrum of biological activity, including anticonvulsant effects, appear promising for the creation of new pharmaceutical agents capable of meeting the needs of military medicine. The purpose of the study was to investigate the biological activity of 2-[5-(furan-2-yl)-4-phenyl-4H-1,2,4-triazol-3-ylthio]-1-(4-chlorophenyl)ethanone using computer-based predictive methods. This approach allows to determine the presence of new types of activity, which could expand scientific research pathways and establish a promising direction for further testing of this molecule. Materials and methods. Molecular docking was performed using Autodock 4.2.6. For screening, the crystallographic structures of GABAA receptors –“4COF,” “6D6T,” and “6X3U” - obtained from the RCSB Protein Data Bank were used. Visualization of the results was conducted using Schrödinger Release 2018-1: Schrödinger, LLC, New York, NY, 2018. The grid parameters for binding were 30 Å × 30 Å × 30 Å, and the grid center coordinates were: 4COF (7 Å × 12 Å × 132 Å), 6D6T (119 Å × 181 Å × 126 Å), 6X3U (137 Å × 108 Å × 142 Å), which provided a sufficiently large space to encompass the receptor center. The ADME evaluation was performed using the free SwissADME tool, which is widely used in medicinal chemistry for analyzing pharmacokinetics, bioavailability, and interactions of small molecules with enzymes. This service considers six physicochemical characteristics: lipophilicity, size, polarity, solubility, flexibility and saturation. Each of these characteristics has its own physicochemical range, which is visualized as a pink zone on the radar plot. For a molecule to be considered drug-like, its radar profile must be entirely within this zone. Results. The study of the interaction of the selected compound with GABAA receptors (4COF, 6D6T, 6X3U) demonstrated its ability to stably bind to the active sites of the receptors, as evidenced by binding energies ranging from –6.119 to –8.559 kcal/mol. The main interactions include hydrophobic contacts, hydrogen bonds, and electrostatic interactions, indicating the compound's potential to modulate receptor activity. The high binding energy values, particularly for the 6X3U structure, suggest the possibility of effectively influencing neuronal excitability, which is promising for the development of antiepileptic agents. The obtained results confirm that the selected compound has potential for further research as a candidate for the development of new pharmaceutical drugs. Conclusions. The pharmacokinetic analysis demonstrated favourable bioavailability characteristics of the compound, including optimal lipophilicity, solubility, and molecular size, in accordance with the parameters typical for pharmaceutical drugs. This enhances the prospects for further investigation of the compound in experimental epilepsy models and for the development of new anticonvulsant drugs based on it. The use of computer modelling significantly accelerates the selection of promising compounds, reduces drug development costs, and contributes to the creation of more effective medications for military personnel in the future.

Quinolones represent one of the largest classes of synthetic antibiotics used in both human and veterinary medicine. Since the discovery of nalidixic acid, a substantial body of research has been carried out on quinolones, resulting in the synthesis of several quinolone derivatives with exceptional pharmacology. In addition to their antibacterial action, quinolones have a broad spectrum of diverse biological activities. In this regard, the present review examines the literature of recent years describing synthesis protocols, reactivity and biological properties, with particular emphasis on the antibacterial, antimalarial, antitrypanosomal, antileishmanial, antiviral and anticancer activities of this famous class of molecules. Finally, this review highlights the potential of quinolones as preferred pharmacophores in medicinal chemistry. The aim is to highlight the innovative aspects of the rational design of new therapeutic agents with this structural motif, in the face of emerging antibiotic resistance and the urgent need for new active molecules.

Indole, a privileged heterocyclic nucleus has diverse biological activities and inspired chemists to utilise this skeleton as bioactive moiety to synthesize new compounds possessing pharmacological and biological properties. The beauty of indole moiety is that it provides a privilege scaffold for the discovery of different kinds of more active, less toxic novel drugs with different modes of action. Now it is found an abiding interest in the use of indole derivatives against cancer cells, microbes and different kinds of disorder in the human body. Extensive researches on manifold implication of indole and its derivatives have been going on since long specifically in the field of agrochemicals and pharmaceuticals. The review is intended to give a general overview of the various research activities in this expanding field. Here we have made of attempt in highlighting the synthetic routes and characteristics of indole and its derivatives along with their recent developments in pharmacological potential values.