Cancer is a fatal illness, accounting for millions of deaths worldwide annually. Recent statistics from the International Agency for Research on Cancer (IARC) show that 19.3 million people were diagnosed with cancer in 2020, with 10 million losing their lives as a result of the disease [1]. Major research conducted by the World Health Organization (WHO) revealed that cancer was responsible for about 9.6 million deaths globally in 2018, making it the sixth leading cause of death. The uncontrolled growth of abnormal cells within the body constitutes one of the defining characteristics associated with cancer [2]. Globally, lung, breast, cervical, and prostate tumours were frequent. A recent analysis indicated that lung cancer and BC account for 1.8 million and 0.6 million fatalities, respectively. With one in four women diagnosed with this deadly disease, female breast cancer ranks among the top cancers causing death in women [3]. Three Conventional therapies, including surgery, chemotherapy, and radiation, are significantly accessible for cancer treatment yet, they can seriously damage normal cells [4].

In females, BC accounts for 23 % of all cancer diagnoses and 14 % of all cancer deaths. It is also a malignancy that is diagnosed most frequently and is the leading cause of mortality from cancer. It has also become the foremost cause of cancer-related mortality among females throughout economically developing nations [5]. By 2020, BC had surpassed lung cancer incidence and was the leading cause of cancer-related deaths among women worldwide, according to the IARC. Nearly 2.3 million cases of new cancer are identified annually, 11.7 % of all cancers [6,7]. By 2040, overall BC diagnoses are anticipated to increase by more than 40 % to 3 million per year. Approximately 50 % more deaths will be predicted by 2040, with a total of 1 million [6]. Based on hormonal receptor status, cellular biological indicators, and genetic mutations, BC may be basic or invasive and categorised as Luminal A, B, HER2 overexpression, or TNBC. Environmental factors and dietary habits constitute the predominant causes of breast cancer induction, with minor contributors including virus-mediated genetic abnormalities and others [8]. Dysregulation in BC is mainly caused by proto-oncogene hyperactivation and tumour suppressor gene inactivation [9].

The PI3K-Akt-mTOR signalling pathway serves an essential part in cell cycle progression, cell proliferation, and other biological outcomes, and it is often activated abnormally in a number of human cancers [10,11]. Tumour growth and treatment resistance are both aided by molecular aberrations that activate the PAM pathway. Consequently, this route was extensively used in oncological therapy. Phosphatidylinositol is then phosphorylated by PI3K kinase. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) facilitates the activation of PI3K kinase via its interaction with Akt's pH domain [12]. Phosphorylation of mTOR molecules or the TSC1/2 complex may then trigger Akt to activate the mTOR kinase. Fig. 1 shows the following stimulation of molecules that are downstream through the mTOR kinase [13]. The regulation of cellular metabolism, growth, and survival was dependent on Phosphoinositide 3-kinases (PI3Ks) [14,15]. PI3K activation activates signalling pathways which enhance division, metabolic processes, movement, proliferation of cells, and lifespan [16]. In mammalian organisms, PI3Ks were lipid kinases that were categorised into three separate categories: I, II, and III [17].

Its importance in physiology and disease has been extensively studied. Class I PI3K is a well-studied subtype linked to cancer development and progression [18]. PIK3CA, PIK3CB, and PIK3CD encode catalytic subunit p110 (p110α, p110β, p110γ, or p110δ) and regulatory subunit p85 (p85α, p85β, and p85γ) for Class I PI3Ks. Human malignancies commonly have abnormal activation of the PI3K, PKB/AKT, and mechanistic target of rapamycin pathways, which are essential for cell survival, proliferation, mobility, and metabolic processes [[19], [20], [21]]. Unlike class I PI3K (PIK3C1), class II/III (PIK3C2/3) phosphorylates phosphatidylinositol to generate PI3P, which modulates autophagy and trafficking of vesicles [22,23]. Class II PI3K aids cell motility and angiogenesis. BC becomes more susceptible to chemotherapeutic treatments when PIK3C2 expression was low [24]. PIK3C2 seems less responsive to typical PI3K antagonists. More research will be required to develop targeted PIK3C2 blockers [25,26]. Both autophagy and iron metabolism control, PIK3C3 regulates tumour cell proliferation [27]. The inhibition of PIK3C3 could hinder breast, colorectal, and prostate malignancies during preliminary investigations [28,29]. Abnormal PAM pathway activation frequently leads to excessive cellular proliferation and apoptosis resistance, causing various cancers [30]. Nearly 70 % of BC patients possess PAM pathway dysfunction [31,32].

Alpelisib, Capivasertib, Fulvestrant, Inavolisib, Palbociclib, and Everolimus are among the PI3K/AKT/mTOR inhibitors that have received FDA approval for the management of multiple variants of breast carcinoma. The emergence of resistance to these medications has limited their use, necessitating the exploration of alternatives for a definitive therapy option against BC. Notwithstanding comprehensive studies and rapid advancements in cancer therapy, there exists an urgent need to formulate a novel class of anticancer drugs aimed at targeting breast cancer cells [33]. Compounds with diverse heterocyclic moieties have acquired particular significance in drug analysis for BC. The development of novel bioactive compounds using molecular identification captivates the interest of medicinal chemists. The exploration of the PAM pathway in BC has considerably improved our comprehension of tumour biology. The introduction of sophisticated medicines that emphasise critical components of this system enhances therapy alternatives and yields better patient results [34]. Research has shown that individuals from an ethnic group with only genetic alterations in this system receive the greatest benefit from pharmaceuticals aimed at modulating PI3K, AKT, or mTOR [35]. The present study attempts to evaluate and explain the properties of heterocyclic compounds that exhibit activity against breast carcinoma. Data collection began in 2016 with a comprehensive search of published articles in databases such as Science Direct, PubMed, SciFinder, and Google Scholar. A variety of medications containing heterocyclic moieties are commercially available, as seen in Fig. 2. The figure illustrates the significance of the nucleus, prompting our selection of the heterocyclic nucleus.