Recent Advances on Quinazoline Derivatives: A Potential Bioactive Scaffold in Medicinal Chemistry

: This paper intended to explore and discover recent therapeutic agents in the area of medicinal chemistry for the treatment of various diseases. Heterocyclic compounds represent an important group of biologically active compounds. In the last few years, heterocyclic compounds having quinazoline moiety have drawn immense attention owing to their signiﬁcant biological activities. A diverse range of molecules having quinazoline moiety are reported to show a broad range of medicinal activities like antifungal, antiviral, antidiabetic, anticancer, anti-inﬂammatory, antibacterial, antioxidant and other activities. This study accelerates the designing process to generate a greater number of biologically active candidates.


Introduction
Heterocyclic rings containing nitrogen and sulfur are of much intention as they are therapeutically and pharmacologically more active. These compounds are the building blocks of many pharmaceutical products. Among all heterocyclic moieties, quinazoline has been taken for this review, as quinazoline has a very broad spectrum of pharmacological activities with minimum side effects [1]. Quinazoline is a well known heterocyclic compound having the chemical formula C 8 H 6 N 2 . Quinazoline is a light yellow crystalline solid and is also known as 1,3-diazanaphthalene, which comprises one benzene and one pyrimidine ring. Synthesis of quinazoline was first reported through decarboxylation of 2-carboxy derivative by August Bischler and Lang in 1895 [2]. Anthranilic acid on treatment with amide resulted in 4-oxo-3,4-dihydroquinazolies by Niementowski synthesis [3]. Other isomers of quinazoline are quinoaxoline, cinnoline and phthalizine [4]. Quinazolines are also the building blocks of more than 200 natural alkaloids isolated from plants, microorganisms and animals [5,6]. Vasicine (±) (peganine) was the first known quinazoline alkaloid which was isolated from Adhatoda vasica in 1888. It is highly effective against bronchodilator activity [7].
Quinazolinone is one of the derivatives of quinazoline which is active like quinazoline [8]. Based on the substitution pattern, quinazolinones are further divided into subcategories such as 2-quinazolinone (a) and 4-quinazolinone (b) as shown in Figure 1 [9].
Thus, quinazoline is a structure of great interest in the area of pharmaceutical chemistry, featuring in various drugs, clinical candidates and bioactive molecules. The focus of this review is on potential biological activity of quinazoline derivatives. This review article will be advantageous in providing information regarding the latest developments on quinazoline analogs having completely different pharmacological activities like antitumor, antimicrobial, antimalarial, antiviral and antidiabetic, etc. This review will also be quinazoline analogs having completely different pharmacological activities like antitumor, antimicrobial, antimalarial, antiviral and antidiabetic, etc. This review will also be stimulating for the researchers to design, synthesize and enhance the potentiality of vital medicine having quinazoline moieties for the treatment of assorted diseases in the future.

Synthesis Routes of Quinazoline
There are several reported methods to synthesize quinazoline moiety.
ChemEngineering 2021, 5, x FOR PEER REVIEW 2 of 29 quinazoline analogs having completely different pharmacological activities like antitumor, antimicrobial, antimalarial, antiviral and antidiabetic, etc. This review will also be stimulating for the researchers to design, synthesize and enhance the potentiality of vital medicine having quinazoline moieties for the treatment of assorted diseases in the future.

Synthesis Routes of Quinazoline
There are several reported methods to synthesize quinazoline moiety.
(i) Niementowski quinazoline synthesis: Anthranilic acid when treated with formamide at higher temperature resulted 3,4 dihydro-4-oxaquinazoline ( Figure 2) [10].  quinazoline analogs having completely different pharmacological activities like antitumor, antimicrobial, antimalarial, antiviral and antidiabetic, etc. This review will also be stimulating for the researchers to design, synthesize and enhance the potentiality of vital medicine having quinazoline moieties for the treatment of assorted diseases in the future.

Synthesis Routes of Quinazoline
There are several reported methods to synthesize quinazoline moiety.

Pharmacological Significance of Quinazoline Derivatives
Quinazoline and quinazolinone based molecules are significant in pharmaceutical chemistry because of their broad range of medicinal and therapeutic activities, such as anti-tumor, antifungal, anti-inflammatory, antibacterial, antioxidant and other activities. Certain synthesized molecules having quinazoline moieties exhibited anticancer activity, such as epidermal growth factor receptor (EGFR) inhibitory activity with half maximal inhibitory concentration (IC50) values equal to known drugs.

Pharmacological Significance of Quinazoline Derivatives
Quinazoline and quinazolinone based molecules are significant in pharmaceutical chemistry because of their broad range of medicinal and therapeutic activities, such as anti-tumor, antifungal, anti-inflammatory, antibacterial, antioxidant and other activities. Certain synthesized molecules having quinazoline moieties exhibited anticancer activity, such as epidermal growth factor receptor (EGFR) inhibitory activity with half maximal inhibitory concentration (IC50) values equal to known drugs.

Pharmacological Significance of Quinazoline Derivatives
Quinazoline and quinazolinone based molecules are significant in pharmaceutical chemistry because of their broad range of medicinal and therapeutic activities, such as anti-tumor, antifungal, anti-inflammatory, antibacterial, antioxidant and other activities. Certain synthesized molecules having quinazoline moieties exhibited anticancer activity, such as epidermal growth factor receptor (EGFR) inhibitory activity with half maximal inhibitory concentration (IC50) values equal to known drugs.
There are several approved drugs in the market with quinazoline moiety, as shown in Table 1.

Pharmacological Significance of Quinazoline Derivatives
Quinazoline and quinazolinone based molecules are significant in pharmaceutical chemistry because of their broad range of medicinal and therapeutic activities, such as anti-tumor, antifungal, anti-inflammatory, antibacterial, antioxidant and other activities. Certain synthesized molecules having quinazoline moieties exhibited anticancer activity, such as epidermal growth factor receptor (EGFR) inhibitory activity with half maximal inhibitory concentration (IC 50 ) values equal to known drugs.

Quinazoline as Anti-Tumor Agents
Quinazoline and its numerous derivatives can be extracted from plants. The substituted quinazoline has been widely used as an anti-tumor agent due to its structure-activity relationship. Many studies reported several synthesis derivatives of quinazoline and elucidated their promising characteristics as anticancer agents against various tumors. Recent developments in quinazoline derivatives are highlighted in this study.
A series of quinazoline derivatives was prepared by the structural modification at the 6-and 7-position of quinazoline core. The most potent derivative ( Table 2, Compound 4) obtained in this series was observed as a multi-kinase inhibitor and also shows effective cellular anti-proliferative activity against several cancer cell lines [29].
Quinazoline derivatives bearing benzene sulfonamides moieties were prepared and tested for antitumor activity by El-Azab et al. [30]. Synthesized compounds ( Table 2, Compound 5) were found most potent against carbonic anhydrase (CA) inhibitory activity. Activity was compared with the reference drug acetazolamide, a typical sulphonamide inhibitor.
Rahmannejadi et al. [31] synthesized a very new series of bis-quinazolin-4(3H)-ones derivatives and evaluated them for their antitumor activity. Bromo derivatives of this compound were found to have the maximum potential of cytotoxic activity over dibromo or dimethyl compounds. Most competent derivatives are shown in Table 2, Compound 6.
Cancer of large intestine [25]

Quinazoline as Anti-Tumor Agents
Quinazoline and its numerous derivatives can be extracted from plants. The substituted quinazoline has been widely used as an anti-tumor agent due to its structure-activity relationship. Many studies reported several synthesis derivatives of quinazoline and elucidated their promising characteristics as anticancer agents against various tumors. Recent developments in quinazoline derivatives are highlighted in this study.
A series of quinazoline derivatives was prepared by the structural modification at the 6-and 7-position of quinazoline core. The most potent derivative ( Table 2, Compound 4) obtained in this series was observed as a multi-kinase inhibitor and also shows effective cellular anti-proliferative activity against several cancer cell lines [29].
Quinazoline derivatives bearing benzene sulfonamides moieties were prepared and tested for antitumor activity by El-Azab et al. [30]. Synthesized compounds ( Table 2, Compound 5) were found most potent against carbonic anhydrase (CA) inhibitory activity. Activity was compared with the reference drug acetazolamide, a typical sulphonamide inhibitor.
Rahmannejadi et al. [31] synthesized a very new series of bis-quinazolin-4(3H)-ones derivatives and evaluated them for their antitumor activity. Bromo derivatives of this compound were found to have the maximum potential of cytotoxic activity over dibromo or dimethyl compounds. Most competent derivatives are shown in Table 2, Compound 6.

, Compound 7).
A series of 3-methyl-quinazolinone derivatives was designed and prepared by Le et al. [33]. Antitumor activity of synthesized compounds was tested in three human cancer cell lines including A549, PC-3 and SMMC-7721. Selected compounds as in Table 2 -quinazolin-4-one, were found to be the most potent inhibitor of EGFR with an IC 50 value of 10 nM.
One more series of quinazoline derivatives has been synthesised by alkylation, and hydrazinolysis of the inherent thioxo group gives corresponding thioethers [36]. Compounds shown (Table 2, Compound 11) had great activity against the used cell-lines with IC 50 values ranging from 1.85 to 2.81 lM against HeLa and MDA-MB231 cells, respectively.
Effective for the treatment of hyperproliferative diseases such as cancer [45]   Type 1 receptor tyrosine kinase inhibitors .

Quinazoline as Anti-Viral
Antiviral activity of a molecule is entirely related to the compounds that either kill the virus or reduce its growth rate without displaying any toxicity to the host and nearby tissues. The various derivatives of quinazoline have been explored to show significant antiviral activities as discussed.
To eliminate the side effects and disadvantages of HCV, Rothan et al. [48] designed a new series of quinazoline derivatives and evaluated their biological activity as antiviral agents. Synthesized compounds as in Table 3, Compound 2, show remarkable activity against HCV NS3-4Apro with a considerable reduction in Renilla luciferase (Rluc) activities at 40 µM.

Quinazoline as Anti-Bacterial
Various researches have confirmed the antibacterial activity of quinazolinone d atives higher than of standard drugs. This is due to the structural features of these an which is the main reason of the interest for research in this area.
Kumar et al. [55] synthesized novel series of 4-amino -N-(phenyl)benzenesul mides derivative and evaluated their antimicrobial activity. Chloro-derivative of sy sized compounds as in Table 4, Compound 2, were found to be most potent cand against the gram-negative bacteria strain.
A new class of compounds was synthesized by Chang et. al. [57]. The synthe compound 3-(2-(4-ethynylstyryl)-4-oxoquinazolin-3(4H)-yl) benzoic acid as in Tab Compound 4, is a highly effective antibiotic against gram positive bacteria, viz., S. a (i) Hepatitis C Virus (ii) Japanese Encephalitis Virus - [53] Quinazoline artemisinin hybrids were synthesized and evaluated for their in vitro biological activity. Novel quinazoline artemisinin hybrids were synthesized and evaluated for their antiviral activity [50]. Synthesized hybrids as in Table 3, Compounds 4(a) and (b), were found to have most potent activity against cytomegalovirus having EC 50 = 0.15−0.21 µM. These compounds were compared with ganciclovir having EC 50 = 2.6 µM and found to be superior by a factor of 12−17.

Quinazoline as Anti-Bacterial
Various researches have confirmed the antibacterial activity of quinazolinone derivatives higher than of standard drugs. This is due to the structural features of these analogs which is the main reason of the interest for research in this area.

Quinazoline as Anti-Bacterial
Various researches have confirmed the antibacterial activity of quinazolinone de atives higher than of standard drugs. This is due to the structural features of these anal which is the main reason of the interest for research in this area.

Quinazoline as Anti-Tubercular Activity
TB is one of the most prevalent and contagious diseases. Quinazoline molecules been explored as a potent scaffold for anti-tubercular activity. The following studie plored the strong approach of quinazoline derivatives as biologically active antituber agents. Gram-positive Bacteria (ii) Gram-negative Bacteria MIC in mg/mL (i) 6.25 (ii) 3.12 [55] 3.

Quinazoline as Anti-Tubercular Activity
TB is one of the most prevalent and contagious diseases. Quinazoline molecules been explored as a potent scaffold for anti-tubercular activity. The following studie plored the strong approach of quinazoline derivatives as biologically active antituber agents.
Staphylococcus aureus M (RSA) (gram positive bacteria) - [57] Kumar et al. [55] synthesized novel series of 4-amino-N-(phenyl)benzenesulfonamides derivative and evaluated their antimicrobial activity. Chloro-derivative of synthesized compounds as in Table 4, Compound 2, were found to be most potent candidate against the gram-negative bacteria strain.

Quinazoline as Anti-Tubercular Activity
TB is one of the most prevalent and contagious diseases. Quinazoline molecules have been explored as a potent scaffold for anti-tubercular activity. The following studies explored the strong approach of quinazoline derivatives as biologically active antitubercular agents.
Lupien et al. have synthesized new derivatives of 2-Ethylthio-4-methylamino quinazoline and evaluated for their biological activity against Mycobacterium tuberculosi (M. tb) [60]. It was concluded that quinazoline based derivatives are a potent moiety fo the tuberculosis drug targeting (Table 5, Compound 3).

Quinazoline as Anti-Oxidant Activity
Excessive formation of free radicals due to oxidative stress need to be supressed i the human body. Developments of antioxidative agents are the one major necessity in th area of drug designing, as the antioxidant can defend the body due to the damage by fre radicals. Antioxidative properties of quinazolines derivative is a recent and emerging con cern.
Synthesis of novel 2-thioxobenzo quinazoline with their analogs was performed b Salahi et al. [61] and tested as anti-oxidant. Synthesized benzoquinazolines as shown i Table 6, Compound 1, were found to have high DPPH and free radical scavenging activi ties along with the reduction competence. Butylated hydroxyl toluene (BHT) was take as the reference compound.
Lupien et al. have synthesized new derivatives of 2-Ethylthio-4-methylaminoquinazoline and evaluated for their biological activity against Mycobacterium tuberculosis (M. tb) [60]. It was concluded that quinazoline based derivatives are a potent moiety for the tuberculosis drug targeting (Table 5, Compound 3).

Quinazoline as Anti-Oxidant Activity
Excessive formation of free radicals due to oxidative stress need to be supressed in the human body. Developments of antioxidative agents are the one major necessity in the area of drug designing, as the antioxidant can defend the body due to the damage by free radicals. Antioxidative properties of quinazolines derivative is a recent and emerging concern.
Synthesis of novel 2-thioxobenzo quinazoline with their analogs was performed by Salahi et al. [61] and tested as anti-oxidant. Synthesized benzoquinazolines as shown in Table 6, Compound 1, were found to have high DPPH and free radical scavenging activities along with the reduction competence. Butylated hydroxyl toluene (BHT) was taken as the reference compound.
Lupien et al. have synthesized new derivatives of 2-Ethylthio-4-methylaminoquinazoline and evaluated for their biological activity against Mycobacterium tuberculosis (M. tb) [60]. It was concluded that quinazoline based derivatives are a potent moiety for the tuberculosis drug targeting (Table 5, Compound 3).

Quinazoline as Anti-Oxidant Activity
Excessive formation of free radicals due to oxidative stress need to be supressed in the human body. Developments of antioxidative agents are the one major necessity in the area of drug designing, as the antioxidant can defend the body due to the damage by free radicals. Antioxidative properties of quinazolines derivative is a recent and emerging con cern.
Synthesis of novel 2-thioxobenzo quinazoline with their analogs was performed by Salahi et al. [61] and tested as anti-oxidant. Synthesized benzoquinazolines as shown in Table 6, Compound 1, were found to have high DPPH and free radical scavenging activities along with the reduction competence. Butylated hydroxyl toluene (BHT) was taken as the reference compound.
Novel analogs of 2-phenoxy benzo triazoloquinazoline were prepared by Almehizia et al. [62]. These compounds were tested for their biological activity as anti-oxidant by using three different assays. The results showed that benzotriazoloquinazoline derivative 6-(trifluoromethyl)-N-(4-oxothiazolidin-3-yl)quinazoline-2-carboxamide derivatives ( Table 5, Compound 2) have been designed as an antitubercular agent for the inhibition of DprE1 [59]. Compounds with nitro and hydroxyl groups have maximum antitubercular activity against Mycobacterium tuberculosis H37RV.
Lupien et al. have synthesized new derivatives of 2-Ethylthio-4-methylaminoquinazoline and evaluated for their biological activity against Mycobacterium tuberculosis (M. tb) [60]. It was concluded that quinazoline based derivatives are a potent moiety for the tuberculosis drug targeting (Table 5, Compound 3).

Quinazoline as Anti-Oxidant Activity
Excessive formation of free radicals due to oxidative stress need to be supressed in the human body. Developments of antioxidative agents are the one major necessity in the area of drug designing, as the antioxidant can defend the body due to the damage by free radicals. Antioxidative properties of quinazolines derivative is a recent and emerging concern.
Synthesis of novel 2-thioxobenzo quinazoline with their analogs was performed by Salahi et al. [61] and tested as anti-oxidant. Synthesized benzoquinazolines as shown in Table 6, Compound 1, were found to have high DPPH and free radical scavenging activities along with the reduction competence. Butylated hydroxyl toluene (BHT) was taken as the reference compound. A new series of 2, 3 substituted quinazolinones analogs were synthesized and tested for their biological activity [64]. Antioxidant activity was tested by DPPH-radical-scav enging, reducing power and total antioxidant status (TAS) assay. Synthesized compound as shown in Table 6, Compound 4, possess antioxidant activity.   A new series of 2, 3 substituted quinazolinones analogs were synthesized and tested for their biological activity [64]. Antioxidant activity was tested by DPPH-radical-scav enging, reducing power and total antioxidant status (TAS) assay. Synthesized compounds as shown in Table 6, Compound 4, possess antioxidant activity.

Quinazoline as Anti-Convulsant
Novel 2,3-disubstituted-4-(3H) quinazolinone derivatives were prepared and evalu ated for their anti-convulsant activity [65]. The synthesized drug was used against elec troshock-induced seizures and PTZ-induced clonic seizures. Compounds as in Table 7 Compound 1, were screened for anticonvulsant activity and found to be the most poten anti-convulsant and carbamazepine.  [64] Novel analogs of 2-phenoxy benzo triazoloquinazoline were prepared by Almehizia et al. [62]. These compounds were tested for their biological activity as anti-oxidant by using three different assays. The results showed that benzotriazoloquinazoline derivative has good antioxidant activities with the capability of scavenging the free radicals. The synthesized compounds as shown in Table 6, Compound 2, were found to exhibit the highest antioxidant activity. BHT was taken as the reference agent.
A new series of 2, 3 substituted quinazolinones analogs were synthesized and tested for their biological activity [64]. Antioxidant activity was tested by DPPH-radical-scavenging, reducing power and total antioxidant status (TAS) assay. Synthesized compounds as shown in Table 6, Compound 4, possess antioxidant activity.

Quinazoline as Anti-Convulsant
Novel 2,3-disubstituted-4-(3H) quinazolinone derivatives were prepared and evaluated for their anti-convulsant activity [65]. The synthesized drug was used against electroshock-induced seizures and PTZ-induced clonic seizures. Compounds as in Table 7, Compound 1, were screened for anticonvulsant activity and found to be the most potent anti-convulsant and carbamazepine.

Quinazoline as Anti-Convulsant
Novel 2,3-disubstituted-4-(3H) quinazolinone derivatives were prepared and evalu ated for their anti-convulsant activity [65]. The synthesized drug was used against elec troshock-induced seizures and PTZ-induced clonic seizures. Compounds as in Table 7 Compound 1, were screened for anticonvulsant activity and found to be the most poten anti-convulsant and carbamazepine.

Quinazoline as Anti-Convulsant
Novel 2,3-disubstituted-4-(3H) quinazolinone derivatives were prepared and evalu ated for their anti-convulsant activity [65]. The synthesized drug was used against elec troshock-induced seizures and PTZ-induced clonic seizures. Compounds as in Table 7 Compound 1, were screened for anticonvulsant activity and found to be the most poten anti-convulsant and carbamazepine.   Showed activity on promastigotes and intracellular amastigotes [75] 12.

Quinazoline as Anti-Inflammatory Agents
Stavytskyi et al. [66] synthesized substituted pyrrolo-quinazoline derivatives an tested their biological activity as an anti-inflammatory activity with reference to dicl fenac. The synthesized compound as in Table 7, Compound 2, was found to be the mo potent anti-inflammatory agent. Bansal et al. [67] designed and synthesized a novel cla of 4-amino quinazoline derivatives and tested them for their anti-inflammatory activit Showed activity on promastigotes and intracellular amastigotes [75] 12.

Quinazoline as Anti-Inflammatory Agents
Stavytskyi et al. [66] synthesized substituted pyrrolo-quinazoline derivatives an tested their biological activity as an anti-inflammatory activity with reference to dic fenac. The synthesized compound as in Table 7, Compound 2, was found to be the mo potent anti-inflammatory agent. Bansal et al. [67] designed and synthesized a novel cla of 4-amino quinazoline derivatives and tested them for their anti-inflammatory activi Showed activity on promastigotes and intracellular amastigotes [75] 12.

Quinazoline as Anti-Inflammatory Agents
Stavytskyi et al. [66] synthesized substituted pyrrolo-quinazoline derivatives a tested their biological activity as an anti-inflammatory activity with reference to dic fenac. The synthesized compound as in Table 7, Compound 2, was found to be the mo potent anti-inflammatory agent. Bansal et al. [67] designed and synthesized a novel cla of 4-amino quinazoline derivatives and tested them for their anti-inflammatory activi Showed activity on promastigotes and intracellular amastigotes [75] 12.

Quinazoline as Anti-Inflammatory Agents
Stavytskyi et al. [66] synthesized substituted pyrrolo-quinazoline derivatives an tested their biological activity as an anti-inflammatory activity with reference to dicl fenac. The synthesized compound as in Table 7, Compound 2, was found to be the mo potent anti-inflammatory agent. Bansal et al. [67] designed and synthesized a novel cla of 4-amino quinazoline derivatives and tested them for their anti-inflammatory activi Evaluated as Antiparasite agents Showed activity on promastigotes and intracellular amastigotes [75] 12 Showed activity on promastigotes and intracellular amastigotes [75] 12.

Quinazoline as Anti-Inflammatory Agents
Stavytskyi et al. [66] synthesized substituted pyrrolo-quinazoline derivatives a tested their biological activity as an anti-inflammatory activity with reference to dic fenac. The synthesized compound as in Table 7, Compound 2, was found to be the mo potent anti-inflammatory agent. Bansal et al. [67] designed and synthesized a novel cla of 4-amino quinazoline derivatives and tested them for their anti-inflammatory activi

Quinazoline as Anti-Inflammatory Agents
Stavytskyi et al. [66] synthesized substituted pyrrolo-quinazoline derivatives and tested their biological activity as an anti-inflammatory activity with reference to diclofenac. The synthesized compound as in Table 7, Compound 2, was found to be the most potent anti-inflammatory agent. Bansal et al. [67] designed and synthesized a novel class of 4-amino quinazoline derivatives and tested them for their anti-inflammatory activity. The synthesized compound N-(4-fluorophenyl)quinazolin-4-amine as shown in Table 7, Compound 3, was found to be the most potent compound which showed high anti-inflammatory activity. The synthesized compound was compared to standard drug indomethacin.

Quinazoline as Sirtuin Modulating Agents
Sirtuin modulating compounds were designed by Oalmann et al. [68] to increase the life of cells.

Quinazoline as Antidiabetic Agents
A series with 3-substituted quinazoline-2,4 diones scaffolds was synthesized and evaluated for their biological activity as antidiabetic agents [69]. Synthesized compounds 3-propylquinazoline-2,4(1H,3H)-dione (a) and 3-cyclohexylquinazoline-2,4(1H,3H)-dione (b) as shown in Table 7, Compound 5, were found to have highly alpha-amylase and alphaglucosidase inhibitory activity in molecular docking studies artemia salina assay. These active compounds have shown unusual intermolecular interaction in the pocked site of the studied enzymes. Results showed that the synthesised compound is an inhibitor of the enzymes responsible for diabetic conditions like alpha-amylase and/or alpha-glucosidase.

Quinazoline as Antifungal Agents
Zhang et al. [70] synthesized a series of quinazolinone derivatives and evaluated them for their biological activity as antifungal agents. Synthesized compounds as shown in Table 7, Compound 6, were found to be highly potent as antifungal agents.
Agarwal et al. synthesized a series of quinazoline derivatives and evaluated them for their biological activity. The synthesized compound as shown in Table 7, Compounds 8, had shown strong antifungal activity compared to standard drug fluconazole [72].

Conclusions
Quinazoline is a structure of great interest in the area of pharmaceutical chemistry, featuring various drugs, clinical candidates and bioactive molecules. The focus of this review was on the potential biological activity of quinazoline derivatives. This review is additionally useful in providing information regarding the latest developments in quinazoline analogs having completely different pharmacological activity like antitumor, antimicrobial, antimalarial, antiviral and antidiabetic, etc. Diversified biological activities of quinazolinebased drugs comprise the role of substituents along with the position at quinazoline moiety, which gives an insight to understanding the drug and target relation. Therefore, critical and deep research for the various substituents of quinazoline is crucial for potential drug development. This review will provide substantial benefit to scientists for the design and synthesis of quinazoline moiety-based drugs for the safe treatment of various fetal diseases in future.